Trophoblast cell surface antigen 2 (Trop2) is a widely expressed glycoprotein and an epithelial cell adhesion molecule (EpCAM) family member. Although initially identified as a transmembrane protein, other subcellular localizations and processed forms were described. Its congenital mutations cause a gelatinous drop-like corneal dystrophy, a disease characterized by loss of barrier function in corneal epithelial cells. Trop2 is considered a stem cell marker and its expression associates with regenerative capacity in various tissues. Trop2 overexpression was described in tumors of different origins; however, functional studies revealed both oncogenic and tumor suppressor roles. Nevertheless, therapeutic potential of Trop2 was recognized and clinical studies with drug-antibody conjugates have been initiated in various cancer types. One of these agents, sacituzumab govitecan, has been recently granted an accelerated approval for therapy of metastatic triple-negative breast cancer. In this article, we review the current knowledge about the yet controversial function of Trop2 in homeostasis and pathology.

Center of Biomolecular and Cellular Engineering International Clinical Research Center St Anne's University Hospital 656 91 Brno Czech Republic

Department of Cytokinetics Institute of Biophysics of the Czech Academy of Sciences 612 65 Brno Czech Republic

Department of Experimental Biology Faculty of Science Masaryk University 625 00 Brno Czech Republic

Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center New York NY 10065 USA

Research Centre for Toxic Compounds in the Environment Faculty of Science Masaryk University 625 00 Brno Czech Republic

Zobrazit více v PubMed

Lipinski M., Parks D.R., Rouse R.V., Herzenberg L.A. Human trophoblast cell-surface antigens defined by monoclonal antibodies. Proc. Natl. Acad. Sci. USA. 1981;78:5147–5150. doi: 10.1073/pnas.78.8.5147. PubMed DOI PMC

Cubas R., Li M., Chen C., Yao Q. Trop2: A possible therapeutic target for late stage epithelial carcinomas. Biochim. Biophys. Acta. 2009;1796:309–314. doi: 10.1016/j.bbcan.2009.08.001. PubMed DOI

Calabrese G., Crescenzi C., Morizio E., Palka G., Guerra E., Alberti S. Assignment of TACSTD1 (alias TROP1, M4S1) to human chromosome 2p21 and refinement of mapping of TACSTD2 (alias TROP2, M1S1) to human chromosome 1p32 by in situ hybridization. Cytogenet. Cell Genet. 2001;92:164–165. doi: 10.1159/000056891. PubMed DOI

Linnenbach A.J., Wojcierowski J., Wu S.A., Pyrc J.J., Ross A.H., Dietzschold B., Speicher D., Koprowski H. Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733. Proc. Natl. Acad. Sci. USA. 1989;86:27–31. doi: 10.1073/pnas.86.1.27. PubMed DOI PMC

McDougall A.R.A., Tolcos M., Hooper S.B., Cole T.J., Wallace M.J. Trop2: From development to disease. Dev. Dyn. 2015;244:99–109. doi: 10.1002/dvdy.24242. PubMed DOI

Szala S., Froehlich M., Scollon M., Kasai Y., Steplewski Z., Koprowski H., Linnenbach A.J. Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2. Proc. Natl. Acad. Sci. USA. 1990;87:3542–3546. doi: 10.1073/pnas.87.9.3542. PubMed DOI PMC

Linnenbach A.J., Seng B.A., Wu S., Robbins S., Scollon M., Pyrc J.J., Druck T., Huebner K. Retroposition in a family of carcinoma-associated antigen genes. Mol. Cell. Biol. 1993;13:1507–1515. doi: 10.1128/MCB.13.3.1507. PubMed DOI PMC

El Sewedy T., Fornaro M., Alberti S. Cloning of the murine TROP2 gene: Conservation of a PIP2-binding sequence in the cytoplasmic domain of TROP-2. Int. J. Cancer. 1998;75:324–330. doi: 10.1002/(SICI)1097-0215(19980119)75:2<324::AID-IJC24>3.0.CO;2-B. PubMed DOI

UniProt: A worldwide hub of protein knowledge. Nucleic Acids Res. 2019;47:D506–D515. doi: 10.1093/nar/gky1049. PubMed DOI PMC

Basu A., Goldenberg D.M., Stein R. The epithelial/carcinoma antigen EGP-1, recognized by monoclonal antibody RS7-3G11, is phosphorylated on serine 303. Int. J. Cancer. 1995;62:472–479. doi: 10.1002/ijc.2910620419. PubMed DOI

Pavšič M., Ilc G., Vidmar T., Plavec J., Lenarčič B. The cytosolic tail of the tumor marker protein Trop2—A structural switch triggered by phosphorylation. Sci. Rep. 2015;5:10324. doi: 10.1038/srep10324. PubMed DOI PMC

Vidmar T., Pavšič M., Lenarčič B. Biochemical and preliminary X-ray characterization of the tumor-associated calcium signal transducer 2 (Trop2) ectodomain. Protein Expr. Purif. 2013;91:69–76. doi: 10.1016/j.pep.2013.07.006. PubMed DOI

Mori Y., Akita K., Ojima K., Iwamoto S., Yamashita T., Morii E., Nakada H. Trophoblast cell surface antigen 2 (Trop-2) phosphorylation by protein kinase C α/δ (PKCα/δ) enhances cell motility. J. Biol. Chem. 2019;294:11513–11524. doi: 10.1074/jbc.RA119.008084. PubMed DOI PMC

Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Global, In Vivo, and Site-Specific Phosphorylation Dynamics in Signaling Networks. Cell. 2006;127:635–648. doi: 10.1016/j.cell.2006.09.026. PubMed DOI

Stepan L.P., Trueblood E.S., Hale K., Babcook J., Borges L., Sutherland C.L. Expression of Trop2 cell surface glycoprotein in normal and tumor tissues: Potential implications as a cancer therapeutic target. J. Histochem. Cytochem. 2011;59:701–710. doi: 10.1369/0022155411410430. PubMed DOI PMC

Trerotola M., Cantanelli P., Guerra E., Tripaldi R., Aloisi A.L., Bonasera V., Lattanzio R., de Lange R., Weidle U.H., Piantelli M., et al. Upregulation of Trop-2 quantitatively stimulates human cancer growth. Oncogene. 2013;32:222–233. doi: 10.1038/onc.2012.36. PubMed DOI

McDougall A.R.A., Hooper S.B., Zahra V.A., Sozo F., Lo C.Y., Cole T.J., Doran T., Wallace M.J. The oncogene Trop2 regulates fetal lung cell proliferation. Am. J. Physiol. Lung Cell. Mol. Physiol. 2011;301:L478–L489. doi: 10.1152/ajplung.00063.2011. PubMed DOI

Sozo F., Wallace M.J., Zahra V.A., Filby C.E., Hooper S.B. Gene expression profiling during increased fetal lung expansion identifies genes likely to regulate development of the distal airways. Physiol. Genomics. 2006;24:105–113. doi: 10.1152/physiolgenomics.00148.2005. PubMed DOI

Mustata R.C., Vasile G., Fernandez-Vallone V., Strollo S., Lefort A., Libert F., Monteyne D., Pérez-Morga D., Vassart G., Garcia M.-I. Identification of Lgr5-independent spheroid-generating progenitors of the mouse fetal intestinal epithelium. Cell Rep. 2013;5:421–432. doi: 10.1016/j.celrep.2013.09.005. PubMed DOI

Vallone V.F., Leprovots M., Strollo S., Vasile G., Lefort A., Libert F., Vassart G., Garcia M.-I. Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage. Development. 2016;143:1452–1463. doi: 10.1242/dev.131490. PubMed DOI PMC

Sun W., Wilhelmina Aalders T., Oosterwijk E. Identification of potential bladder progenitor cells in the trigone. Dev. Biol. 2014;393:84–92. doi: 10.1016/j.ydbio.2014.06.018. PubMed DOI

Tsukahara Y., Tanaka M., Miyajima A. TROP2 expressed in the trunk of the ureteric duct regulates branching morphogenesis during kidney development. PLoS ONE. 2011;6:e28607. doi: 10.1371/journal.pone.0028607. PubMed DOI PMC

McDougall A.R.A., Wiradjaja V., Azhan A., Li A., Hale N., Wlodek M.E., Hooper S.B., Wallace M.J., Tolcos M. Intrauterine Growth Restriction Alters the Postnatal Development of the Rat Cerebellum. Dev. Neurosci. 2017;39:215–227. doi: 10.1159/000470902. PubMed DOI

Memarzadeh S., Zong Y., Janzen D.M., Goldstein A.S., Cheng D., Kurita T., Schafenacker A.M., Huang J., Witte O.N. Cell-autonomous activation of the PI3-kinase pathway initiates endometrial cancer from adult uterine epithelium. Proc. Natl. Acad. Sci. USA. 2010;107:17298–17303. doi: 10.1073/pnas.1012548107. PubMed DOI PMC

Li T., Su Y., Yu X., Mouniir D.S.A., Masau J.F., Wei X., Yang J. Trop2 Guarantees Cardioprotective Effects of Cortical Bone-Derived Stem Cells on Myocardial Ischemia/Reperfusion Injury. Cell Transplant. 2018;27:1256–1268. doi: 10.1177/0963689718786882. PubMed DOI PMC

Yang J., Zhu Z., Wang H., Li F., Du X., Ma R.Z. Trop2 regulates the proliferation and differentiation of murine compact-bone derived MSCs. Int. J. Oncol. 2013;43:859–867. doi: 10.3892/ijo.2013.1987. PubMed DOI

Grünherz L., Prein C., Winkler T., Kirsch M., Hopfner U., Streichert T., Clausen-Schaumann H., Zustin J., Kirchhof K., Morlock M.M., et al. Osteoidosis leads to altered differentiation and function of osteoclasts. J. Cell. Mol. Med. 2020;24:5665–5674. doi: 10.1111/jcmm.15227. PubMed DOI PMC

Goldstein A.S., Lawson D.A., Cheng D., Sun W., Garraway I.P., Witte O.N. Trop2 identifies a subpopulation of murine and human prostate basal cells with stem cell characteristics. Proc. Natl. Acad. Sci. USA. 2008;105:20882–20887. doi: 10.1073/pnas.0811411106. PubMed DOI PMC

Kahounová Z., Remšík J., Fedr R., Bouchal J., Mičková A., Slabáková E., Binó L., Hampl A., Souček K. Slug-expressing mouse prostate epithelial cells have increased stem cell potential. Stem Cell Res. 2020;46:101844. doi: 10.1016/j.scr.2020.101844. PubMed DOI

Crowell P.D., Fox J.J., Hashimoto T., Diaz J.A., Navarro H.I., Henry G.H., Feldmar B.A., Lowe M.G., Garcia A.J., Wu Y.E., et al. Expansion of Luminal Progenitor Cells in the Aging Mouse and Human Prostate. Cell Rep. 2019;28:1499–1510. doi: 10.1016/j.celrep.2019.07.007. PubMed DOI PMC

Okabe M., Tsukahara Y., Tanaka M., Suzuki K., Saito S., Kamiya Y., Tsujimura T., Nakamura K., Miyajima A. Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver. Dev. Camb. Engl. 2009;136:1951–1960. doi: 10.1242/dev.031369. PubMed DOI

Liu Q., Li H., Wang Q., Zhang Y., Wang W., Dou S., Xiao W. Increased expression of TROP2 in airway basal cells potentially contributes to airway remodeling in chronic obstructive pulmonary disease. Respir. Res. 2016;17:159. doi: 10.1186/s12931-016-0463-z. PubMed DOI PMC

McDougall A.R.A., Hooper S.B., Zahra V.A., Cole T.J., Lo C.Y., Doran T., Wallace M.J. Trop2 regulates motility and lamellipodia formation in cultured fetal lung fibroblasts. Am. J. Physiol. Lung Cell. Mol. Physiol. 2013;305:L508–L521. doi: 10.1152/ajplung.00160.2012. PubMed DOI

Aizarani N., Saviano A., Sagar, Mailly L., Durand S., Herman J.S., Pessaux P., Baumert T.F., Grün D. A human liver cell atlas reveals heterogeneity and epithelial progenitors. Nature. 2019;572:199–204. doi: 10.1038/s41586-019-1373-2. PubMed DOI PMC

Wang J., Zhang K., Grabowska D., Li A., Dong Y., Day R., Humphrey P., Lewis J., Kladney R.D., Arbeit J.M., et al. Loss of Trop2 promotes carcinogenesis and features of epithelial to mesenchymal transition in squamous cell carcinoma. Mol. Cancer Res. MCR. 2011;9:1686–1695. doi: 10.1158/1541-7786.MCR-11-0241. PubMed DOI PMC

Lei Z., Maeda T., Tamura A., Nakamura T., Yamazaki Y., Shiratori H., Yashiro K., Tsukita S., Hamada H. EpCAM contributes to formation of functional tight junction in the intestinal epithelium by recruiting claudin proteins. Dev. Biol. 2012;371:136–145. doi: 10.1016/j.ydbio.2012.07.005. PubMed DOI

Guerra E., Lattanzio R., La Sorda R., Dini F., Tiboni G.M., Piantelli M., Alberti S. mTrop1/Epcam Knockout Mice Develop Congenital Tufting Enteropathy through Dysregulation of Intestinal E-cadherin/β-catenin. PLoS ONE. 2012;7:e49302. doi: 10.1371/journal.pone.0049302. PubMed DOI PMC

Mueller J.L., McGeough M.D., Peña C.A., Sivagnanam M. Functional consequences of EpCam mutation in mice and men. Am. J. Physiol. Gastrointest. Liver Physiol. 2014;306:G278–G288. doi: 10.1152/ajpgi.00286.2013. PubMed DOI PMC

Sivagnanam M., Mueller J.L., Lee H., Chen Z., Nelson S.F., Turner D., Zlotkin S.H., Pencharz P.B., Ngan B.-Y., Libiger O., et al. Identification of EpCAM as the Gene for Congenital Tufting Enteropathy. Gastroenterology. 2008;135:429–437. doi: 10.1053/j.gastro.2008.05.036. PubMed DOI PMC

Balzar M., Winter M.J., de Boer C.J., Litvinov S.V. The biology of the 17–1A antigen (Ep-CAM) J. Mol. Med. 1999;77:699–712. doi: 10.1007/s001099900038. PubMed DOI

Nakato G., Morimura S., Lu M., Feng X., Wu C., Udey M.C. Amelioration of Congenital Tufting Enteropathy in EpCAM (TROP1)-Deficient Mice via Heterotopic Expression of TROP2 in Intestinal Epithelial Cells. Cells. 2020;9:1847. doi: 10.3390/cells9081847. PubMed DOI PMC

Tsujikawa M., Kurahashi H., Tanaka T., Nishida K., Shimomura Y., Tano Y., Nakamura Y. Identification of the gene responsible for gelatinous drop-like corneal dystrophy. Nat. Genet. 1999;21:420–423. doi: 10.1038/7759. PubMed DOI

Nagahara Y., Tsujikawa M., Takigawa T., Xu P., Kai C., Kawasaki S., Nakatsukasa M., Inatomi T., Kinoshita S., Nishida K. A novel mutation in gelatinous drop-like corneal dystrophy and functional analysis. Hum. Genome Var. 2019;6:33. doi: 10.1038/s41439-019-0060-z. PubMed DOI PMC

Ide T., Nishida K., Maeda N., Tsujikawa M., Yamamoto S., Watanabe H., Tano Y. A spectrum of clinical manifestations of gelatinous drop-like corneal dystrophy in japan. Am. J. Ophthalmol. 2004;137:1081–1084. doi: 10.1016/j.ajo.2004.01.048. PubMed DOI

Takaoka M., Nakamura T., Ban Y., Kinoshita S. Phenotypic investigation of cell junction-related proteins in gelatinous drop-like corneal dystrophy. Investig. Ophthalmol. Vis. Sci. 2007;48:1095–1101. doi: 10.1167/iovs.06-0740. PubMed DOI

Nakatsukasa M., Kawasaki S., Yamasaki K., Fukuoka H., Matsuda A., Tsujikawa M., Tanioka H., Nagata-Takaoka M., Hamuro J., Kinoshita S. Tumor-associated calcium signal transducer 2 is required for the proper subcellular localization of claudin 1 and 7: Implications in the pathogenesis of gelatinous drop-like corneal dystrophy. Am. J. Pathol. 2010;177:1344–1355. doi: 10.2353/ajpath.2010.100149. PubMed DOI PMC

Xu P., Kai C., Kawasaki S., Kobayashi Y., Yamamoto K., Tsujikawa M., Hayashi R., Nishida K. A New in Vitro Model of GDLD by Knocking Out TACSTD2 and Its Paralogous Gene EpCAM in Human Corneal Epithelial Cells. Transl. Vis. Sci. Technol. 2018;7:30. doi: 10.1167/tvst.7.6.30. PubMed DOI PMC

Nübel T., Preobraschenski J., Tuncay H., Weiss T., Kuhn S., Ladwein M., Langbein L., Zöller M. Claudin-7 regulates EpCAM-mediated functions in tumor progression. Mol. Cancer Res. MCR. 2009;7:285–299. doi: 10.1158/1541-7786.MCR-08-0200. PubMed DOI

Sekhar V., Pollicino T., Diaz G., Engle R.E., Alayli F., Melis M., Kabat J., Tice A., Pomerenke A., Altan-Bonnet N., et al. Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma. PLoS Pathog. 2018;14:e1006916. doi: 10.1371/journal.ppat.1006916. PubMed DOI PMC

Wu C.-J., Lu M., Feng X., Nakato G., Udey M.C. Matriptase Cleaves EpCAM and TROP2 in Keratinocytes, Destabilizing Both Proteins and Associated Claudins. Cells. 2020;9:1027. doi: 10.3390/cells9041027. PubMed DOI PMC

Wu C.-J., Feng X., Lu M., Morimura S., Udey M.C. Matriptase-mediated cleavage of EpCAM destabilizes claudins and dysregulates intestinal epithelial homeostasis. J. Clin. Investig. 2017;127:623–634. doi: 10.1172/JCI88428. PubMed DOI PMC

Kamble P.R., Rane S., Breed A.A., Joseph S., Mahale S.D., Pathak B.R. Proteolytic cleavage of Trop2 at Arg87 is mediated by matriptase and regulated by Val194. FEBS Lett. 2020;594:3156–3169. doi: 10.1002/1873-3468.13899. PubMed DOI

Ripani E., Sacchetti A., Corda D., Alberti S. Human Trop-2 is a tumor-associated calcium signal transducer. Int. J. Cancer. 1998;76:671–676. doi: 10.1002/(SICI)1097-0215(19980529)76:5<671::AID-IJC10>3.0.CO;2-7. PubMed DOI

Cheng N., Li H., Luo J. Trop2 promotes proliferation, invasion and EMT of nasopharyngeal carcinoma cells through the NF-κB pathway. RSC Adv. 2017;7:53087–53096. doi: 10.1039/C7RA09915K. PubMed DOI PMC

Gu Q.-Z., Nijiati A., Gao X., Tao K.-L., Li C.-D., Fan X.-P., Tian Z. TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling. Mol. Med. Rep. 2018;18:1782–1788. doi: 10.3892/mmr.2018.9083. PubMed DOI

Li X., Teng S., Zhang Y., Zhang W., Zhang X., Xu K., Yao H., Yao J., Wang H., Liang X., et al. TROP2 promotes proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT. Oncotarget. 2017;8:47052–47063. doi: 10.18632/oncotarget.16789. PubMed DOI PMC

Sun X., Xing G., Zhang C., Lu K., Wang Y., He X. Knockdown of Trop2 inhibits proliferation and migration and induces apoptosis of endometrial cancer cells via AKT/β-catenin pathway. Cell Biochem. Funct. 2020 doi: 10.1002/cbf.3450. PubMed DOI

Tang G., Tang Q., Jia L., Chen Y., Lin L., Kuai X., Gong A., Feng Z. TROP2 increases growth and metastasis of human oral squamous cell carcinoma through activation of the PI3K/Akt signaling pathway. Int. J. Mol. Med. 2019;44:2161–2170. doi: 10.3892/ijmm.2019.4378. PubMed DOI PMC

Guerra E., Trerotola M., Tripaldi R., Aloisi A.L., Simeone P., Sacchetti A., Relli V., D’Amore A., La Sorda R., Lattanzio R., et al. Trop-2 Induces Tumor Growth Through AKT and Determines Sensitivity to AKT Inhibitors. Clin. Cancer Res. 2016;22:4197–4205. doi: 10.1158/1078-0432.CCR-15-1701. PubMed DOI

Cubas R., Zhang S., Li M., Chen C., Yao Q. Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway. Mol. Cancer. 2010;9:253. doi: 10.1186/1476-4598-9-253. PubMed DOI PMC

Guan H., Guo Z., Liang W., Li H., Wei G., Xu L., Xiao H., Li Y. Trop2 enhances invasion of thyroid cancer by inducing MMP2 through ERK and JNK pathways. BMC Cancer. 2017;17:486. doi: 10.1186/s12885-017-3475-2. PubMed DOI PMC

Liu T., Liu Y., Bao X., Tian J., Liu Y., Yang X. Overexpression of TROP2 predicts poor prognosis of patients with cervical cancer and promotes the proliferation and invasion of cervical cancer cells by regulating ERK signaling pathway. PLoS ONE. 2013;8:e75864. doi: 10.1371/journal.pone.0075864. PubMed DOI PMC

Redlich N., Robinson A.M., Nickel K.P., Stein A.P., Wheeler D.L., Adkins D.R., Uppaluri R., Kimple R.J., Van Tine B.A., Michel L.S. Anti-Trop2 blockade enhances the therapeutic efficacy of ErbB3 inhibition in head and neck squamous cell carcinoma. Cell Death Dis. 2018;9:5. doi: 10.1038/s41419-017-0029-0. PubMed DOI PMC

Wang F., Liu X., Yang P., Guo L., Liu C., Li H., Long S., Shen Y., Wan H. Loss of TACSTD2 contributed to squamous cell carcinoma progression through attenuating TAp63-dependent apoptosis. Cell Death Dis. 2014;5:e1133. doi: 10.1038/cddis.2014.96. PubMed DOI PMC

Zhang K., Jones L., Lim S., Maher C.A., Adkins D., Lewis J., Kimple R.J., Fertig E.J., Chung C.H., Van Tine B.A., et al. Loss of Trop2 causes ErbB3 activation through a neuregulin-1-dependent mechanism in the mesenchymal subtype of HNSCC. Oncotarget. 2014;5:9281–9294. doi: 10.18632/oncotarget.2423. PubMed DOI PMC

Zhao W., Jia L., Kuai X., Tang Q., Huang X., Yang T., Qiu Z., Zhu J., Huang J., Huang W., et al. The role and molecular mechanism of Trop2 induced epithelial-mesenchymal transition through mediated β-catenin in gastric cancer. Cancer Med. 2019;8:1135–1147. doi: 10.1002/cam4.1934. PubMed DOI PMC

Stoyanova T., Goldstein A.S., Cai H., Drake J.M., Huang J., Witte O.N. Regulated proteolysis of Trop2 drives epithelial hyperplasia and stem cell self-renewal via β-catenin signaling. Genes Dev. 2012;26:2271–2285. doi: 10.1101/gad.196451.112. PubMed DOI PMC

Hou J., Lv A., Deng Q., Zhang G., Hu X., Cui H. TROP2 promotes the proliferation and metastasis of glioblastoma cells by activating the JAK2/STAT3 signaling pathway. Oncol. Rep. 2019;41:753–764. doi: 10.3892/or.2018.6859. PubMed DOI PMC

Trerotola M., Ganguly K.K., Fazli L., Fedele C., Lu H., Dutta A., Liu Q., De Angelis T., Riddell L.W., Riobo N.A., et al. Trop-2 is up-regulated in invasive prostate cancer and displaces FAK from focal contacts. Oncotarget. 2015;6:14318–14328. doi: 10.18632/oncotarget.3960. PubMed DOI PMC

Trerotola M., Jernigan D.L., Liu Q., Siddiqui J., Fatatis A., Languino L.R. Trop-2 promotes prostate cancer metastasis by modulating β(1) integrin functions. Cancer Res. 2013;73:3155–3167. doi: 10.1158/0008-5472.CAN-12-3266. PubMed DOI PMC

Trerotola M., Li J., Alberti S., Languino L.R. Trop-2 inhibits prostate cancer cell adhesion to fibronectin through the β1 integrin-RACK1 axis. J. Cell. Physiol. 2012;227:3670–3677. doi: 10.1002/jcp.24074. PubMed DOI PMC

Webb D.J., Donais K., Whitmore L.A., Thomas S.M., Turner C.E., Parsons J.T., Horwitz A.F. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat. Cell Biol. 2004;6:154–161. doi: 10.1038/ncb1094. PubMed DOI

Lin J.-C., Wu Y.-Y., Wu J.-Y., Lin T.-C., Wu C.-T., Chang Y.-L., Jou Y.-S., Hong T.-M., Yang P.-C. TROP2 is epigenetically inactivated and modulates IGF-1R signalling in lung adenocarcinoma. EMBO Mol. Med. 2012;4:472–485. doi: 10.1002/emmm.201200222. PubMed DOI PMC

Pak M.G., Shin D.H., Lee C.H., Lee M.K. Significance of EpCAM and TROP2 expression in non-small cell lung cancer. World J. Surg. Oncol. 2012;10:53. doi: 10.1186/1477-7819-10-53. PubMed DOI PMC

Sawanyawisuth K., Tantapotinan N., Wongkham C., Riggins G.J., Kraiklang R., Wongkham S., Puapairoj A. Suppression of trophoblast cell surface antigen 2 enhances proliferation and migration in liver fluke-associated cholangiocarcinoma. Ann. Hepatol. 2016;15:71–81. doi: 10.5604/16652681.1184223. PubMed DOI

Kobayashi H., Minami Y., Anami Y., Kondou Y., Iijima T., Kano J., Morishita Y., Tsuta K., Hayashi S., Noguchi M. Expression of the GA733 gene family and its relationship to prognosis in pulmonary adenocarcinoma. Virchows Arch. Int. J. Pathol. 2010;457:69–76. doi: 10.1007/s00428-010-0930-8. PubMed DOI

Sin S.T.K., Li Y., Liu M., Ma S., Guan X.-Y. TROP-2 exhibits tumor suppressive functions in cervical cancer by dual inhibition of IGF-1R and ALK signaling. Gynecol. Oncol. 2018;152:185–193. doi: 10.1016/j.ygyno.2018.10.039. PubMed DOI

Eyvazi S., Farajnia S., Dastmalchi S., Kanipour F., Zarredar H., Bandehpour M. Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update. Curr. Cancer Drug Targets. 2018;18:857–868. doi: 10.2174/1568009618666180102102311. PubMed DOI

Keller L., Werner S., Pantel K. Biology and clinical relevance of EpCAM. Cell Stress. 2019;3:165–180. doi: 10.15698/cst2019.06.188. PubMed DOI PMC

Martowicz A., Seeber A., Untergasser G. The role of EpCAM in physiology and pathology of the epithelium. Histol. Histopathol. 2016;31:349–355. doi: 10.14670/HH-11-678. PubMed DOI

Herreros-Pomares A., Aguilar-Gallardo C., Calabuig-Fariñas S., Sirera R., Jantus-Lewintre E., Camps C. EpCAM duality becomes this molecule in a new Dr. Jekyll and Mr. Hyde tale. Crit. Rev. Oncol. Hematol. 2018;126:52–63. doi: 10.1016/j.critrevonc.2018.03.006. PubMed DOI

Fong D., Moser P., Krammel C., Gostner J.M., Margreiter R., Mitterer M., Gastl G., Spizzo G. High expression of TROP2 correlates with poor prognosis in pancreatic cancer. Br. J. Cancer. 2008;99:1290–1295. doi: 10.1038/sj.bjc.6604677. PubMed DOI PMC

Fong D., Spizzo G., Gostner J.M., Gastl G., Moser P., Krammel C., Gerhard S., Rasse M., Laimer K. TROP2: A novel prognostic marker in squamous cell carcinoma of the oral cavity. Mod. Pathol. 2008;21:186–191. doi: 10.1038/modpathol.3801001. PubMed DOI

Hsu E.-C., Rice M.A., Bermudez A., Marques F.J.G., Aslan M., Liu S., Ghoochani A., Zhang C.A., Chen Y.-S., Zlitni A., et al. Trop2 is a driver of metastatic prostate cancer with neuroendocrine phenotype via PARP1. Proc. Natl. Acad. Sci. USA. 2020;117:2032–2042. doi: 10.1073/pnas.1905384117. PubMed DOI PMC

Mühlmann G., Spizzo G., Gostner J., Zitt M., Maier H., Moser P., Gastl G., Zitt M., Müller H.M., Margreiter R., et al. TROP2 expression as prognostic marker for gastric carcinoma. J. Clin. Pathol. 2009;62:152–158. doi: 10.1136/jcp.2008.060590. PubMed DOI

Ning S., Guo S., Xie J., Xu Y., Lu X., Chen Y. TROP2 correlates with microvessel density and poor prognosis in hilar cholangiocarcinoma. J. Gastrointest. Surg. 2013;17:360–368. doi: 10.1007/s11605-012-2105-1. PubMed DOI

Zhao W., Kuai X., Zhou X., Jia L., Wang J., Yang X., Tian Z., Wang X., Lv Q., Wang B., et al. Trop2 is a potential biomarker for the promotion of EMT in human breast cancer. Oncol. Rep. 2018;40:759–766. doi: 10.3892/or.2018.6496. PubMed DOI

Sin S.T.K., Li Y., Liu M., Yuan Y.-F., Ma S., Guan X.-Y. Down-regulation of TROP-2 Predicts Poor Prognosis of Hepatocellular Carcinoma Patients. Hepatol. Commun. 2018;2:1408–1414. doi: 10.1002/hep4.1242. PubMed DOI PMC

Ambrogi F., Fornili M., Boracchi P., Trerotola M., Relli V., Simeone P., La Sorda R., Lattanzio R., Querzoli P., Pedriali M., et al. Trop-2 is a determinant of breast cancer survival. PLoS ONE. 2014;9:e96993. doi: 10.1371/journal.pone.0096993. PubMed DOI PMC

Zhao W., Zhu H., Zhang S., Yong H., Wang W., Zhou Y., Wang B., Wen J., Qiu Z., Ding G., et al. Trop2 is overexpressed in gastric cancer and predicts poor prognosis. Oncotarget. 2016;7:6136–6145. doi: 10.18632/oncotarget.6733. PubMed DOI PMC

Riera K.M., Jang B., Min J., Roland J.T., Yang Q., Fesmire W.T., Camilleri-Broet S., Ferri L., Kim W.H., Choi E., et al. Trop2 is upregulated in the transition to dysplasia in the metaplastic gastric mucosa. J. Pathol. 2020;251:336–347. doi: 10.1002/path.5469. PubMed DOI PMC

Addati T., Achille G., Centrone M., Petroni S., Popescu O., Russo S., Grammatica L., Simone G. TROP-2 expression in papillary thyroid cancer: A preliminary cyto-histological study. Cytopathology. 2015;26:303–311. doi: 10.1111/cyt.12196. PubMed DOI

Bychkov A., Sampatanukul P., Shuangshoti S., Keelawat S. TROP-2 immunohistochemistry: A highly accurate method in the differential diagnosis of papillary thyroid carcinoma. Pathology. 2016;48:425–433. doi: 10.1016/j.pathol.2016.04.002. PubMed DOI

Simms A., Jacob R.P., Cohen C., Siddiqui M.T. TROP-2 expression in papillary thyroid carcinoma: Potential Diagnostic Utility. Diagn. Cytopathol. 2016;44:26–31. doi: 10.1002/dc.23382. PubMed DOI

Fang Y.J., Lu Z.H., Wang G.Q., Pan Z.Z., Zhou Z.W., Yun J.P., Zhang M.F., Wan D.S. Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer. Int. J. Colorectal Dis. 2009;24:875–884. doi: 10.1007/s00384-009-0725-z. PubMed DOI

Ohmachi T., Tanaka F., Mimori K., Inoue H., Yanaga K., Mori M. Clinical Significance of TROP2 Expression in Colorectal Cancer. Clin. Cancer Res. 2006;12:3057–3063. doi: 10.1158/1078-0432.CCR-05-1961. PubMed DOI

Jiang A., Gao X., Zhang D., Zhang L., Lu H. Expression and clinical significance of the Trop-2 gene in advanced non-small cell lung carcinoma. Oncol. Lett. 2013;6:375–380. doi: 10.3892/ol.2013.1368. PubMed DOI PMC

Mito R., Matsubara E., Komohara Y., Shinchi Y., Sato K., Yoshii D., Ohnishi K., Fujiwara Y., Tomita Y., Ikeda K., et al. Clinical impact of TROP2 in non-small lung cancers and its correlation with abnormal p53 nuclear accumulation. Pathol. Int. 2020;70:187–294. doi: 10.1111/pin.12911. PubMed DOI

Li Z., Jiang X., Zhang W. TROP2 overexpression promotes proliferation and invasion of lung adenocarcinoma cells. Biochem. Biophys. Res. Commun. 2016;470:197–204. doi: 10.1016/j.bbrc.2016.01.032. PubMed DOI

Lin H., Huang J.-F., Qiu J.-R., Zhang H.-L., Tang X.-J., Li H., Wang C.-J., Wang Z.-C., Feng Z.-Q., Zhu J. Significantly upregulated TACSTD2 and Cyclin D1 correlate with poor prognosis of invasive ductal breast cancer. Exp. Mol. Pathol. 2013;94:73–78. doi: 10.1016/j.yexmp.2012.08.004. PubMed DOI

Bignotti E., Todeschini P., Calza S., Falchetti M., Ravanini M., Tassi R.A., Ravaggi A., Bandiera E., Romani C., Zanotti L., et al. Trop-2 overexpression as an independent marker for poor overall survival in ovarian carcinoma patients. Eur. J. Cancer. 2010;46:944–953. doi: 10.1016/j.ejca.2009.12.019. PubMed DOI

Varughese J., Cocco E., Bellone S., Bellone M., Todeschini P., Carrara L., Schwartz P.E., Rutherford T.J., Pecorelli S., Santin A.D. High-grade, chemotherapy-resistant primary ovarian carcinoma cell lines overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody. Gynecol. Oncol. 2011;122:171–177. doi: 10.1016/j.ygyno.2011.03.002. PubMed DOI PMC

Perrone E., Lopez S., Zeybek B., Bellone S., Bonazzoli E., Pelligra S., Zammataro L., Manzano A., Manara P., Bianchi A., et al. Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer. Front. Oncol. 2020;10 doi: 10.3389/fonc.2020.00118. PubMed DOI PMC

Avellini C., Licini C., Lazzarini R., Procopio A.D., Muzzonigro G., Tossetta G., Mazzucchelli R., Gesuita R., Castellucci M., Olivieri F., et al. Expression of Trop2 in bladder cancer is modulated by miR125b: In vivo and in vitro analyses. Ital. J. Anat. Embryol. 2015;120:46. doi: 10.13128/IJAE-16888. DOI

Chen M.-B., Wu H.-F., Zhan Y., Fu X.-L., Wang A.-K., Wang L.-S., Lei H.-M. Prognostic value of TROP2 expression in patients with gallbladder cancer. Tumor Biol. 2014;35:11565–11569. doi: 10.1007/s13277-014-2469-9. PubMed DOI

Varughese J., Cocco E., Bellone S., Ratner E., Silasi D.-A., Azodi M., Schwartz P.E., Rutherford T.J., Buza N., Pecorelli S., et al. Cervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti-Trop-2 antibody. Am. J. Obstet. Gynecol. 2011;205:567.e1–567.e7. doi: 10.1016/j.ajog.2011.06.093. PubMed DOI PMC

Zeybek B., Manzano A., Bianchi A., Bonazzoli E., Bellone S., Buza N., Hui P., Lopez S., Perrone E., Manara P., et al. Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Sci. Rep. 2020;10:973. doi: 10.1038/s41598-020-58009-3. PubMed DOI PMC

Varughese J., Cocco E., Bellone S., de Leon M., Bellone M., Todeschini P., Schwartz P.E., Rutherford T.J., Pecorelli S., Santin A.D. Uterine serous papillary carcinomas overexpress human trophoblast-cell-surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized anti-Trop-2 monoclonal antibody. Cancer. 2011;117:3163–3172. doi: 10.1002/cncr.25891. PubMed DOI PMC

Han C., Perrone E., Zeybek B., Bellone S., Tymon-Rosario J., Altwerger G., Menderes G., Feinberg J., Haines K., Muller Karger M.E., et al. In vitro and in vivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Gynecol. Oncol. 2020;156:430–438. doi: 10.1016/j.ygyno.2019.11.018. PubMed DOI

Lopez S., Perrone E., Bellone S., Bonazzoli E., Zeybek B., Han C., Tymon-Rosario J., Altwerger G., Menderes G., Bianchi A., et al. Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas. Oncotarget. 2020;11:560–570. doi: 10.18632/oncotarget.27342. PubMed DOI PMC

Bignotti E., Ravaggi A., Romani C., Falchetti M., Lonardi S., Facchetti F., Pecorelli S., Varughese J., Cocco E., Bellone S., et al. Trop-2 overexpression in poorly differentiated endometrial endometrioid carcinoma: Implications for immunotherapy with hRS7, a humanized anti-trop-2 monoclonal antibody. Int. J. Gynecol. Cancer. 2011;21:1613–1621. doi: 10.1097/IGC.0b013e318228f6da. PubMed DOI PMC

Bignotti E., Zanotti L., Calza S., Falchetti M., Lonardi S., Ravaggi A., Romani C., Todeschini P., Bandiera E., Tassi R.A., et al. Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma. BMC Clin. Pathol. 2012;12:22. doi: 10.1186/1472-6890-12-22. PubMed DOI PMC

Guan G.-F., Zhang D.-J., Wen L.-J., Yu D.-J., Zhao Y., Zhu L., Guo Y.-Y., Zheng Y. Prognostic value of TROP2 in human nasopharyngeal carcinoma. Int. J. Clin. Exp. Pathol. 2015;8:10995–11004. PubMed PMC

Tang G., Tang Q., Jia L., Xia S., Li J., Chen Y., Li H., Ding X., Wang F., Hou D., et al. High expression of TROP2 is correlated with poor prognosis of oral squamous cell carcinoma. Pathol. Res. Pract. 2018;214:1606–1612. doi: 10.1016/j.prp.2018.07.017. PubMed DOI

Jia L., Wang T., Ding G., Kuai X., Wang X., Wang B., Zhao W., Zhao Y. Trop2 inhibition of P16 expression and the cell cycle promotes intracellular calcium release in OSCC. Int. J. Biol. Macromol. 2020;164:2409–2417. doi: 10.1016/j.ijbiomac.2020.07.234. PubMed DOI

Zhang B., Gao S., Li R., Li Y., Cao R., Cheng J., Guo Y., Wang E., Huang Y., Zhang K. Tissue mechanics and expression of TROP2 in oral squamous cell carcinoma with varying differentiation. BMC Cancer. 2020;20:815. doi: 10.1186/s12885-020-07257-7. PubMed DOI PMC

Nakashima K., Shimada H., Ochiai T., Kuboshima M., Kuroiwa N., Okazumi S., Matsubara H., Nomura F., Takiguchi M., Hiwasa T. Serological identification of TROP2 by recombinant cDNA expression cloning using sera of patients with esophageal squamous cell carcinoma. Int. J. Cancer. 2004;112:1029–1035. doi: 10.1002/ijc.20517. PubMed DOI

Hao Y., Zhang D., Guo Y., Fu Z., Yu D., Guan G. miR-488-3p sponged by circ-0000495 and mediated upregulation of TROP2 in head and neck squamous cell carcinoma development. J. Cancer. 2020;11:3375–3386. doi: 10.7150/jca.40339. PubMed DOI PMC

Wu H., Xu H., Zhang S., Wang X., Zhu H., Zhang H., Zhu J., Huang J. Potential therapeutic target and independent prognostic marker of TROP2 in laryngeal squamous cell carcinoma. Head Neck. 2013;35:1373–1378. doi: 10.1002/hed.23138. PubMed DOI

Salerno E.P., Bedognetti D., Mauldin I.S., Deacon D.H., Shea S.M., Pinczewski J., Obeid J.M., Coukos G., Wang E., Gajewski T.F., et al. Human melanomas and ovarian cancers overexpressing mechanical barrier molecule genes lack immune signatures and have increased patient mortality risk. Oncoimmunology. 2016;5:e1240857. doi: 10.1080/2162402X.2016.1240857. PubMed DOI PMC

Chen R., Lu M., Wang J., Zhang D., Lin H., Zhu H., Zhang W., Xiong L., Ma J., Mao Y., et al. Increased expression of Trop2 correlates with poor survival in extranodal NK/T cell lymphoma, nasal type. Virchows Arch. Int. J. Pathol. 2013;463:713–719. doi: 10.1007/s00428-013-1475-4. PubMed DOI

Ning S., Liang N., Liu B., Chen X., Pang Q., Xin T. TROP2 expression and its correlation with tumor proliferation and angiogenesis in human gliomas. Neurol. Sci. 2013;34:1745–1750. doi: 10.1007/s10072-013-1326-8. PubMed DOI

Chen X., Pang B., Liang Y., Xu S.-C., Xin T., Fan H.-T., Yu Y.-B., Pang Q. Overexpression of EpCAM and Trop2 in pituitary adenomas. Int. J. Clin. Exp. Pathol. 2014;7:7907–7914. PubMed PMC

Tate J.G., Bamford S., Jubb H.C., Sondka Z., Beare D.M., Bindal N., Boutselakis H., Cole C.G., Creatore C., Dawson E., et al. COSMIC: The Catalogue Of Somatic Mutations In Cancer. Nucleic Acids Res. 2019;47:D941–D947. doi: 10.1093/nar/gky1015. PubMed DOI PMC

Guerra E., Trerotola M., Aloisi A.L., Tripaldi R., Vacca G., La Sorda R., Lattanzio R., Piantelli M., Alberti S. The Trop-2 signalling network in cancer growth. Oncogene. 2013;32:1594–1600. doi: 10.1038/onc.2012.151. PubMed DOI

Wu M., Liu L., Hijazi H., Chan C. A multi-layer inference approach to reconstruct condition-specific genes and their regulation. Bioinformatics. 2013;29:1541–1552. doi: 10.1093/bioinformatics/btt186. PubMed DOI PMC

Hidalgo-Estévez A.M., Stamatakis K., Jiménez-Martínez M., López-Pérez R., Fresno M. Cyclooxygenase 2-Regulated Genes an Alternative Avenue to the Development of New Therapeutic Drugs for Colorectal Cancer. Front. Pharmacol. 2020;11 doi: 10.3389/fphar.2020.00533. PubMed DOI PMC

Zhao P., Zhang Z. TNF-α promotes colon cancer cell migration and invasion by upregulating TROP-2. Oncol. Lett. 2018;15:3820–3827. doi: 10.3892/ol.2018.7735. PubMed DOI PMC

Lokody I.B., Francis J.C., Gardiner J.R., Erler J.T., Swain A. Pten Regulates Epithelial Cytodifferentiation during Prostate Development. PLoS ONE. 2015;10:e0129470. doi: 10.1371/journal.pone.0129470. PubMed DOI PMC

Suraneni M.V., Schneider-Broussard R., Moore J.R., Davis T.C., Maldonado C.J., Li H., Newman R.A., Kusewitt D., Hu J., Yang P., et al. Transgenic expression of 15-lipoxygenase 2 (15-LOX2) in mouse prostate leads to hyperplasia and cell senescence. Oncogene. 2010;29:4261–4275. doi: 10.1038/onc.2010.197. PubMed DOI PMC

Eisenwort G., Jurkin J., Yasmin N., Bauer T., Gesslbauer B., Strobl H. Identification of TROP2 (TACSTD2), an EpCAM-Like Molecule, as a Specific Marker for TGF-β1-Dependent Human Epidermal Langerhans Cells. J. Investig. Dermatol. 2011;131:2049–2057. doi: 10.1038/jid.2011.164. PubMed DOI

Lü J., Izvolsky K.I., Qian J., Cardoso W.V. Identification of FGF10 Targets in the Embryonic Lung Epithelium during Bud Morphogenesis. J. Biol. Chem. 2005;280:4834–4841. doi: 10.1074/jbc.M410714200. PubMed DOI

Liu Q., Luo Q., Ju Y., Song G. Role of the mechanical microenvironment in cancer development and progression. Cancer Biol. Med. 2020;17:282–292. doi: 10.20892/j.issn.2095-3941.2019.0437. PubMed DOI PMC

Nakanishi H., Taccioli C., Palatini J., Fernandez-Cymering C., Cui R., Kim T., Volinia S., Croce C. Loss of miR-125b-1 contributes to head and neck cancer development by dysregulating TACSTD2 and MAPK pathway. Oncogene. 2014;33:702–712. doi: 10.1038/onc.2013.13. PubMed DOI PMC

Avellini C., Licini C., Lazzarini R., Gesuita R., Guerra E., Tossetta G., Castellucci C., Giannubilo S.R., Procopio A., Alberti S., et al. The trophoblast cell surface antigen 2 and miR-125b axis in urothelial bladder cancer. Oncotarget. 2017;8:58642–58653. doi: 10.18632/oncotarget.17407. PubMed DOI PMC

Ibragimova I., de Cáceres I.I., Hoffman A.M., Potapova A., Dulaimi E., Al-Saleem T., Hudes G.R., Ochs M.F., Cairns P. Global Reactivation of Epigenetically Silenced Genes in Prostate Cancer. Cancer Prev. Res. 2010;3:1084–1092. doi: 10.1158/1940-6207.CAPR-10-0039. PubMed DOI PMC

Remšík J., Binó L., Kahounová Z., Kharaishvili G., Šimecková Š., Fedr R., Kucírková T., Lenárt S., Muresan X.M., Slabáková E., et al. Trop-2 plasticity is controlled by epithelial-to-mesenchymal transition. Carcinogenesis. 2018;39:1411–1418. doi: 10.1093/carcin/bgy095. PubMed DOI

Kalluri R., Weinberg R.A. The basics of epithelial-mesenchymal transition. J. Clin. Investig. 2009;119:1420–1428. doi: 10.1172/JCI39104. PubMed DOI PMC

Tsai J.H., Yang J. Epithelial-mesenchymal plasticity in carcinoma metastasis. Genes Dev. 2013;27:2192–2206. doi: 10.1101/gad.225334.113. PubMed DOI PMC

Xu W., Yang Z., Lu N. A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition. Cell Adhes. Migr. 2015;9:317–324. doi: 10.1080/19336918.2015.1016686. PubMed DOI PMC

Zhang L., Yang G., Zhang R., Dong L., Chen H., Bo J., Xue W., Huang Y. Curcumin inhibits cell proliferation and motility via suppression of TROP2 in bladder cancer cells. Int. J. Oncol. 2018;53:515–526. doi: 10.3892/ijo.2018.4423. PubMed DOI PMC

Wang J., Day R., Dong Y., Weintraub S.J., Michel L. Identification of Trop-2 as an oncogene and an attractive therapeutic target in colon cancers. Mol. Cancer Ther. 2008;7:280–285. doi: 10.1158/1535-7163.MCT-07-2003. PubMed DOI

Zimmers S.M., Browne E.P., Williams K.E., Jawale R.M., Otis C.N., Schneider S.S., Arcaro K.F. TROP2 methylation and expression in tamoxifen-resistant breast cancer. Cancer Cell Int. 2018;18:94. doi: 10.1186/s12935-018-0589-9. PubMed DOI PMC

Wu B., Yu C., Zhou B., Huang T., Gao L., Liu T., Yang X. Overexpression of TROP2 promotes proliferation and invasion of ovarian cancer cells. Exp. Ther. Med. 2017;14:1947–1952. doi: 10.3892/etm.2017.4788. PubMed DOI PMC

Xie J., Mølck C., Paquet-Fifield S., Butler L., Australian Prostate Cancer Bioresource E.S., Ventura S., Hollande F. High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells. Oncotarget. 2016;7:44492–44504. doi: 10.18632/oncotarget.9876. PubMed DOI PMC

Kuai X., Jia L., Yang T., Huang X., Zhao W., Zhang M., Chen Y., Zhu J., Feng Z., Tang Q. Trop2 Promotes Multidrug Resistance by Regulating Notch1 Signaling Pathway in Gastric Cancer Cells. Med. Sci. Monit. 2020;26:e919566-1–e919566-9. doi: 10.12659/MSM.919566. PubMed DOI PMC

Wang X., Long M., Dong K., Lin F., Weng Y., Ouyang Y., Liu L., Wei J., Chen X., He T., et al. Chemotherapy agents-induced immunoresistance in lung cancer cells could be reversed by trop-2 inhibition in vitro and in vivo by interaction with MAPK signaling pathway. Cancer Biol. Ther. 2013;14:1123–1132. doi: 10.4161/cbt.26341. PubMed DOI PMC

Frederick B.A., Helfrich B.A., Coldren C.D., Zheng D., Chan D., Bunn P.A., Raben D. Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non–small cell lung carcinoma. Mol. Cancer Ther. 2007;6:1683–1691. doi: 10.1158/1535-7163.MCT-07-0138. PubMed DOI

Ray Chaudhuri A., Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat. Rev. Mol. Cell Biol. 2017;18:610–621. doi: 10.1038/nrm.2017.53. PubMed DOI PMC

Stein R., Chen S., Sharkey R.M., Goldenberg D.M. Murine monoclonal antibodies raised against human non-small cell carcinoma of the lung: Specificity and tumor targeting. Cancer Res. 1990;50:1330–1336. PubMed

Stein R., Basu A., Chen S., Shih L.B., Goldenberg D.M. Specificity and properties of MAb RS7-3G11 and the antigen defined by this pancarcinoma monoclonal antibody. Int. J. Cancer. 1993;55:938–946. doi: 10.1002/ijc.2910550611. PubMed DOI

Stein R., Govindan S.V., Chen S., Reed L., Spiegelman H., Griffiths G.L., Hansen H.J., Goldenberg D.M. Successful therapy of a human lung cancer xenograft using MAb RS7 labeled with residualizing radioiodine. Crit. Rev. Oncol. Hematol. 2001;39:173–180. doi: 10.1016/S1040-8428(01)00106-8. PubMed DOI

Stein R., Chen S., Haim S., Goldenberg D.M. Advantage of yttrium-90-labeled over iodine-131-labeled monoclonal antibodies in the treatment of a human lung carcinoma xenograft. Cancer. 1997;80:2636–2641. doi: 10.1002/(SICI)1097-0142(19971215)80:12+<2636::AID-CNCR39>3.0.CO;2-B. PubMed DOI

Stein R., Goldenberg D.M., Thorpe S.R., Mattes M.J. Advantage of a residualizing iodine radiolabel for radioimmunotherapy of xenografts of human non-small-cell carcinoma of the lung. J. Nucl. Med. 1997;38:391–395. PubMed

Shih L.B., Xuan H., Aninipot R., Stein R., Goldenberg D.M. In Vitro and in Vivo Reactivity of an Internalizing Antibody, RS7, with Human Breast Cancer. Cancer Res. 1995;55:5857s–5863s. PubMed

Chang C.-H., Gupta P., Michel R., Loo M., Wang Y., Cardillo T.M., Goldenberg D.M. Ranpirnase (Frog RNase) Targeted with a Humanized, Internalizing, Anti–Trop-2 Antibody Has Potent Cytotoxicity against Diverse Epithelial Cancer Cells. Mol. Cancer Ther. 2010;9:2276–2286. doi: 10.1158/1535-7163.MCT-10-0338. PubMed DOI

Liu D., Cardillo T.M., Wang Y., Rossi E.A., Goldenberg D.M., Chang C.-H. Trop-2-targeting tetrakis-ranpirnase has potent antitumor activity against triple-negative breast cancer. Mol. Cancer. 2014;13:53. doi: 10.1186/1476-4598-13-53. PubMed DOI PMC

Goldenberg D.M., Cardillo T.M., Govindan S.V., Rossi E.A., Sharkey R.M. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC) Oncotarget. 2015;6:22496–22512. doi: 10.18632/oncotarget.4318. PubMed DOI PMC

Fujita K., Kubota Y., Ishida H., Sasaki Y. Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer. World J. Gastroenterol. 2015;21:12234–12248. doi: 10.3748/wjg.v21.i43.12234. PubMed DOI PMC

Goldenberg D.M., Stein R., Sharkey R.M. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget. 2018;9:28989–29006. doi: 10.18632/oncotarget.25615. PubMed DOI PMC

Goldenberg D.M., Sharkey R.M. Sacituzumab govitecan, a novel, third-generation, antibody-drug conjugate (ADC) for cancer therapy. Expert Opin. Biol. Ther. 2020:1–15. doi: 10.1080/14712598.2020.1757067. PubMed DOI

Starodub A.N., Ocean A.J., Shah M.A., Guarino M.J., Picozzi V.J., Jr., Vahdat L.T., Thomas S.S., Govindan S.V., Maliakal P.P., Wegener W.A., et al. First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Clin. Cancer Res. 2015;21:3870–3878. doi: 10.1158/1078-0432.CCR-14-3321. PubMed DOI PMC

Ocean A.J., Starodub A.N., Bardia A., Vahdat L.T., Isakoff S.J., Guarino M., Messersmith W.A., Picozzi V.J., Mayer I.A., Wegener W.A., et al. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Cancer. 2017;123:3843–3854. doi: 10.1002/cncr.30789. PubMed DOI

Faltas B., Goldenberg D.M., Ocean A.J., Govindan S.V., Wilhelm F., Sharkey R.M., Hajdenberg J., Hodes G., Nanus D.M., Tagawa S.T. Sacituzumab Govitecan, a Novel Antibody--Drug Conjugate, in Patients With Metastatic Platinum-Resistant Urothelial Carcinoma. Clin. Genitourin. Cancer. 2016;14:e75–e79. doi: 10.1016/j.clgc.2015.10.002. PubMed DOI

Tagawa S.T., Petrylak D.P., Grivas P., Agarwal N., Sternberg C.N., Hernandez C., Siemon-Hryczyk P., Goswami T., Loriot Y. TROPHY-U-01: A phase II open-label study of sacituzumab govitecan (IMMU-132) in patients with advanced urothelial cancer after progression on platinum-based chemotherapy and/or anti-PD-1/PD-L1 checkpoint inhibitor therapy. J. Clin. Oncol. 2019;37:TPS3153. doi: 10.1200/JCO.2019.37.15_suppl.TPS3153. DOI

Tagawa S.T., Faltas B., Lam E., Saylor P., Bardia A., Hajdenberg J., Morgans A.K., Lim E., Kalinsky K., Petrylak D.P., et al. Sacituzumab govitecan (IMMU-132) for patients with pretreated metastatic urothelial uancer (UC): Interim results. Ann. Oncol. 2017;28:v301–v302. doi: 10.1093/annonc/mdx371.012. DOI

Gray J.E., Heist R.S., Starodub A.N., Camidge D.R., Kio E.A., Masters G.A., Purcell W.T., Guarino M.J., Misleh J., Schneider C.J., et al. Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2017;23:5711–5719. doi: 10.1158/1078-0432.CCR-17-0933. PubMed DOI

Heist R.S., Guarino M.J., Masters G., Purcell W.T., Starodub A.N., Horn L., Scheff R.J., Bardia A., Messersmith W.A., Berlin J., et al. Therapy of Advanced Non–Small-Cell Lung Cancer With an SN-38-Anti-Trop-2 Drug Conjugate, Sacituzumab Govitecan. J. Clin. Oncol. 2017;35:2790–2797. doi: 10.1200/JCO.2016.72.1894. PubMed DOI

Bardia A., Mayer I.A., Diamond J.R., Moroose R.L., Isakoff S.J., Starodub A.N., Shah N.C., O’Shaughnessy J., Kalinsky K., Guarino M., et al. Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J. Clin. Oncol. 2017;35:2141–2148. doi: 10.1200/JCO.2016.70.8297. PubMed DOI PMC

Bardia A., Mayer I.A., Vahdat L.T., Tolaney S.M., Isakoff S.J., Diamond J.R., O’Shaughnessy J., Moroose R.L., Santin A.D., Abramson V.G., et al. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N. Engl. J. Med. 2019;380:741–751. doi: 10.1056/NEJMoa1814213. PubMed DOI

Bardia A., Diamond J.R., Vahdat L.T., Tolaney S.M., O’Shaughnessy J., Moroose R.L., Mayer I.A., Abramson V.G., Juric D., Sharkey R.M., et al. Efficacy of sacituzumab govitecan (anti-Trop-2-SN-38 antibody-drug conjugate) for treatment-refractory hormone-receptor positive (HR+)/HER2- metastatic breast cancer (mBC) J. Clin. Oncol. 2018;36:1004. doi: 10.1200/JCO.2018.36.15_suppl.1004. DOI

Goldenberg D.M., Sharkey R.M. Antibody-drug conjugates targeting TROP-2 and incorporating SN-38: A case study of anti-TROP-2 sacituzumab govitecan. MAbs. 2019;11:987–995. doi: 10.1080/19420862.2019.1632115. PubMed DOI PMC

Syed Y.Y. Sacituzumab Govitecan: First Approval. Drugs. 2020;80:1019–1025. doi: 10.1007/s40265-020-01337-5. PubMed DOI PMC

King G.T., Eaton K.D., Beagle B.R., Zopf C.J., Wong G.Y., Krupka H.I., Hua S.Y., Messersmith W.A., El-Khoueiry A.B. A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody-drug conjugate in patients with advanced or metastatic solid tumors. Investig. New Drugs. 2018;36:836–847. doi: 10.1007/s10637-018-0560-6. PubMed DOI PMC

Strop P., Tran T.-T., Dorywalska M., Delaria K., Dushin R., Wong O.K., Ho W.-H., Zhou D., Wu A., Kraynov E., et al. RN927C, a Site-Specific Trop-2 Antibody–Drug Conjugate (ADC) with Enhanced Stability, Is Highly Efficacious in Preclinical Solid Tumor Models. Mol. Cancer Ther. 2016;15:2698–2708. doi: 10.1158/1535-7163.MCT-16-0431. PubMed DOI

Lin H., Zhang H., Wang J., Lu M., Zheng F., Wang C., Tang X., Xu N., Chen R., Zhang D., et al. A novel human Fab antibody for Trop2 inhibits breast cancer growth in vitro and in vivo. Int. J. Cancer. 2014;134:1239–1249. doi: 10.1002/ijc.28451. PubMed DOI

Mao Y., Wang X., Zheng F., Wang C., Tang Q., Tang X., Xu N., Zhang H., Zhang D., Xiong L., et al. The tumor-inhibitory effectiveness of a novel anti-Trop2 Fab conjugate in pancreatic cancer. Oncotarget. 2016;7:24810–24823. doi: 10.18632/oncotarget.8529. PubMed DOI PMC

Son S., Shin S., Rao N.V., Um W., Jeon J., Ko H., Deepagan V.G., Kwon S., Lee J.Y., Park J.H. Anti-Trop2 antibody-conjugated bioreducible nanoparticles for targeted triple negative breast cancer therapy. Int. J. Biol. Macromol. 2018;110:406–415. doi: 10.1016/j.ijbiomac.2017.10.113. PubMed DOI

Chang C.-H., Goldenberg D.M. Enhancing the antitumor potency of T cells redirected by bispecific antibodies. Oncoscience. 2017;4:120–121. doi: 10.18632/oncoscience.366. PubMed DOI PMC

Cubas R., Zhang S., Li M., Chen C., Yao Q. Chimeric Trop2 Virus-like Particles: A Potential Immunotherapeutic Approach Against Pancreatic Cancer. J. Immunother. 2011;34:251–263. doi: 10.1097/CJI.0b013e318209ee72. PubMed DOI

Xi W., Ke D., Min L., Lin W., Jiahui Z., Fang L., Zhaowei G., Zhe Z., Xi C., Huizhong Z. Incorporation of CD40 ligand enhances the immunogenicity of tumor-associated calcium signal transducer 2 virus-like particles against lung cancer. Int. J. Mol. Med. 2018;41:3671–3679. doi: 10.3892/ijmm.2018.3570. PubMed DOI

Liu T., Tian J., Chen Z., Liang Y., Liu J., Liu S., Li H., Zhan J., Yang X. Anti-TROP2 conjugated hollow gold nanospheres as a novel nanostructure for targeted photothermal destruction of cervical cancer cells. Nanotechnology. 2014;25:345103. doi: 10.1088/0957-4484/25/34/345103. PubMed DOI

Aryl hydrocarbon receptor as a drug target in advanced prostate cancer therapy - obstacles and perspectives

Orthotopic model for the analysis of melanoma circulating tumor cells

TROP2 Represents a Negative Prognostic Factor in Colorectal Adenocarcinoma and Its Expression Is Associated with Features of Epithelial-Mesenchymal Transition and Invasiveness

ATF2 loss promotes tumor invasion in colorectal cancer cells via upregulation of cancer driver TROP2

TACSTD2 upregulation is an early reaction to lung infection