Extracellular AGR3 regulates breast cancer cells migration via Src signaling

. 2019 Nov ; 18 (5) : 4449-4456. [epub] 20190910

Status PubMed-not-MEDLINE Jazyk angličtina Země Řecko Médium print-electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid31611954

Human anterior gradient proteins AGR2 and AGR3 are overexpressed in a variety of adenocarcinomas and are often secreted in cancer patients' specimens, which suggests a role for AGR proteins in intra and extracellular compartments. Although these proteins exhibit high sequence homology, AGR2 is predominantly described as a pro-oncogene and a potential prognostic biomarker. However, little is known about the function of AGR3. Therefore, the aim of the present study was to investigate the role of AGR3 in breast cancer. The results demonstrated that breast cancer cells secrete AGR3. Furthermore, it was revealed that extracellular AGR3 (eAGR3) regulates tumor cell adhesion and migration. The current study indicated that the pharmacological and genetic perturbation of Src kinase signaling, through treatment with Dasatinib (protein kinase inhibitor) or investigating cells that express a dominant-negative form of Src, significantly abrogated eAGR3-mediated breast cancer cell migration. Therefore, the results indicated that eAGR3 may control tumor cell migration via activation of Src kinases. The results of the present study indicated that eAGR3 may serve as a microenvironmental signaling molecule in tumor-associated processes.

Zobrazit více v PubMed

Fletcher GC, Patel S, Tyson K, Adam PJ, Schenker M, Loader JA, Daviet L, Legrain P, Parekh R, Harris AL, Terrett JA. hAG-2 and hAG-3, human homologues of genes involved in differentiation, are associated with oestrogen receptor-positive breast tumours and interact with metastasis gene C4.4a and dystroglycan. Br J Cancer. 2003;88:579–585. doi: 10.1038/sj.bjc.6600740. PubMed DOI PMC

Higa A, Mulot A, Delom F, Bouchecareilh M, Nguyên DT, Boismenu D, Wise MJ, Chevet E. Role of pro-oncogenic protein disulfide isomerase (PDI) family member anterior gradient 2 (AGR2) in the control of endoplasmic reticulum homeostasis. J Biol Chem. 2011;286:44855–44868. doi: 10.1074/jbc.M111.275529. PubMed DOI PMC

Brychtova V, Mohtar A, Vojtesek B, Hupp TR. Mechanisms of anterior gradient-2 regulation and function in cancer. Semin Cancer Biol. 2015;33:16–24. doi: 10.1016/j.semcancer.2015.04.005. PubMed DOI

Park SW, Zhen G, Verhaeghe C, Nakagami Y, Nguyenvu LT, Barczak AJ, Killeen N, Erle DJ. The protein disulfide isomerase AGR2 is essential for production of intestinal mucus. Proc Natl Acad Sci USA. 2009;106:6950–6955. doi: 10.1073/pnas.0808722106. PubMed DOI PMC

Schroeder BW, Verhaeghe C, Park SW, Nguyenvu LT, Huang X, Zhen G, Erle DJ. AGR2 is induced in asthma and promotes allergen-induced mucin overproduction. Am J Respir Cell Mol Biol. 2012;47:178–185. doi: 10.1165/rcmb.2011-0421OC. PubMed DOI PMC

Norris AM, Gore A, Balboni A, Young A, Longnecker DS, Korc M. AGR2 is a SMAD4-suppressible gene that modulates MUC1 levels and promotes the initiation and progression of pancreatic intraepithelial neoplasia. Oncogene. 2013;32:3867–3876. doi: 10.1038/onc.2012.394. PubMed DOI PMC

Bonser LR, Schroeder BW, Ostrin LA, Baumlin N, Olson JL, Salathe M, Erle DJ. The endoplasmic reticulum resident protein AGR3. Required for regulation of ciliary beat frequency in the airway. Am J Respir Cell Mol Biol. 2015;53:536–543. doi: 10.1165/rcmb.2014-0318OC. PubMed DOI PMC

Gray TA, MacLaine NJ, Michie CO, Bouchalova P, Murray E, Howie J, Hrstka R, Maslon MM, Nenutil R, Vojtesek B, et al. Anterior Gradient-3: A novel biomarker for ovarian cancer that mediates cisplatin resistance in xenograft models. J Immunol Methods. 2012;378:20–32. doi: 10.1016/j.jim.2012.01.013. PubMed DOI

Brychtova V, Zampachova V, Hrstka R, Fabian P, Novak J, Hermanova M, Vojtesek B. Differential expression of anterior gradient protein 3 in intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Exp Mol Pathol. 2014;96:375–381. doi: 10.1016/j.yexmp.2014.04.002. PubMed DOI

Vivekanandan P, Micchelli ST, Torbenson M. Anterior gradient-2 is overexpressed by fibrolamellar carcinomas. Hum Pathol. 2009;40:293–299. doi: 10.1016/j.humpath.2008.08.003. PubMed DOI PMC

Obacz J, Takacova M, Brychtova V, Dobes P, Pastorekova S, Vojtesek B, Hrstka R. The role of AGR2 and AGR3 in cancer: Similar but not identical. Eur J Cell Biol. 2015;94:139–147. doi: 10.1016/j.ejcb.2015.01.002. PubMed DOI

Brychtova V, Vojtesek B, Hrstka R. Anterior gradient 2: A novel player in tumor cell biology. Cancer Lett. 2011;304:1–7. doi: 10.1016/j.canlet.2010.12.023. PubMed DOI

Chevet E, Fessart D, Delom F, Mulot A, Vojtesek B, Hrstka R, Murray E, Gray T, Hupp T. Emerging roles for the pro-oncogenic anterior gradient-2 in cancer development. Oncogene. 2013;32:2499–2509. doi: 10.1038/onc.2012.346. PubMed DOI

Salmans ML, Zhao F, Andersen B. The estrogen-regulated anterior gradient 2 (AGR2) protein in breast cancer: A potential drug target and biomarker. Breast Cancer Res. 2013;15:204. doi: 10.1186/bcr3408. PubMed DOI PMC

Kamal A, Valentijn A, Barraclough R, Rudland P, Rahmatalla N, Martin-Hirsch P, Stringfellow H, Decruze SB, Hapangama DK. High AGR2 protein is a feature of low grade endometrial cancer cells. Oncotarget. 2018;9:31459–31472. doi: 10.18632/oncotarget.25838. PubMed DOI PMC

Bergstrom JH, Berg KA, Rodriguez-Pineiro AM, Stecher B, Johansson ME, Hansson GC. AGR2, an endoplasmic reticulum protein, is secreted into the gastrointestinal mucus. PLoS One. 2014;9:e104186. doi: 10.1371/journal.pone.0104186. PubMed DOI PMC

Edgell TA, Barraclough DL, Rajic A, Dhulia J, Lewis KJ, Armes JE, Barraclough R, Rudland PS, Rice GE, Autelitano DJ. Increased plasma concentrations of anterior gradient 2 protein are positively associated with ovarian cancer. Clin Sci (Lond) 2010;118:717–725. doi: 10.1042/CS20090537. PubMed DOI

Kani K, Malihi PD, Jiang Y, Wang H, Wang Y, Ruderman DL, Agus DB, Mallick P, Gross ME. Anterior gradient 2 (AGR2): Blood-based biomarker elevated in metastatic prostate cancer associated with the neuroendocrine phenotype. Prostate. 2013;73:306–315. doi: 10.1002/pros.22569. PubMed DOI

Garczyk S, von Stillfried S, Antonopoulos W, Hartmann A, Schrauder MG, Fasching PA, Anzeneder T, Tannapfel A, Ergönenc Y, Knüchel R, et al. AGR3 in breast cancer: Prognostic impact and suitable serum-based biomarker for early cancer detection. PLoS One. 2015;10:e0122106. doi: 10.1371/journal.pone.0122106. PubMed DOI PMC

Tian S, Hu J, Tao K, Wang J, Chu Y, Li J, Liu Z, Ding X, Xu L, Li Q, et al. Secreted AGR2 promotes invasion of colorectal cancer cells via Wnt11-mediated non-canonical Wnt signaling. Exp Cell Res. 2018;364:198–207. doi: 10.1016/j.yexcr.2018.02.004. PubMed DOI

Tsuji T, Satoyoshi R, Aiba N, Kubo T, Yanagihara K, Maeda D, Goto A, Ishikawa K, Yashiro M, Tanaka M. Agr2 mediates paracrine effects on stromal fibroblasts that promote invasion by gastric signet-ring carcinoma cells. Cancer Res. 2015;75:356–366. doi: 10.1158/0008-5472.CAN-14-1693. PubMed DOI

Arumugam T, Deng D, Bover L, Wang H, Logsdon CD, Ramachandran V. New blocking antibodies against novel AGR2-C4.4A pathway reduce growth and metastasis of pancreatic tumors and increase survival in mice. Mol Cancer Ther. 2015;14:941–951. doi: 10.1158/1535-7163.MCT-14-0470. PubMed DOI PMC

Fessart D, Domblides C, Avril T, Eriksson LA, Begueret H, Pineau R, Malrieux C, Dugot-Senant N, Lucchesi C, Chevet E, Delom F. Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties. Elife. 2016;5(pii):e13887. doi: 10.7554/eLife.13887. PubMed DOI PMC

Adam PJ, Boyd R, Tyson KL, Fletcher GC, Stamps A, Hudson L, Poyser HR, Redpath N, Griffiths M, Steers G, et al. Comprehensive proteomic analysis of breast cancer cell membranes reveals unique proteins with potential roles in clinical cancer. J Biol Chem. 2003;278:6482–6489. doi: 10.1074/jbc.M210184200. PubMed DOI

Obacz J, Brychtova V, Podhorec J, Fabian P, Dobes P, Vojtesek B, Hrstka R. Anterior gradient protein 3 is associated with less aggressive tumors and better outcome of breast cancer patients. Onco Targets Ther. 2015;8:1523–1532. PubMed PMC

Bu H, Schweiger MR, Manke T, Wunderlich A, Timmermann B, Kerick M, Pasqualini L, Shehu E, Fuchsberger C, Cato AC, Klocker H. Anterior gradient 2 and 3-two prototype androgen-responsive genes transcriptionally upregulated by androgens and by oestrogens in prostate cancer cells. FEBS J. 2013;280:1249–1266. doi: 10.1111/febs.12118. PubMed DOI

King ER, Tung CS, Tsang YT, Zu Z, Lok GT, Deavers MT, Malpica A, Wolf JK, Lu KH, Birrer MJ, et al. The anterior gradient homolog 3 (AGR3) gene is associated with differentiation and survival in ovarian cancer. Am J Surg Pathol. 2011;35:904–912. doi: 10.1097/PAS.0b013e318212ae22. PubMed DOI PMC

Trcka F, Durech M, Man P, Hernychova L, Muller P, Vojtesek B. The assembly and intermolecular properties of the Hsp70-Tomm34-Hsp90 molecular chaperone complex. J Biol Chem. 2014;289:9887–9901. doi: 10.1074/jbc.M113.526046. PubMed DOI PMC

Raetz CR, Ulevitch RJ, Wright SD, Sibley CH, Ding A, Nathan CF. Gram-negative endotoxin: An extraordinary lipid with profound effects on eukaryotic signal transduction. FASEB J. 1991;5:2652–2660. doi: 10.1096/fasebj.5.12.1916089. PubMed DOI

Fessart D, Simaan M, Laporte SA. c-Src regulates clathrin adapter protein 2 interaction with beta-arrestin and the angiotensin II type 1 receptor during clathrin-mediated internalization. Mol Endocrinol. 2005;19:491–503. doi: 10.1210/me.2004-0246. PubMed DOI

Geback T, Schulz MM, Koumoutsakos P, Detmar M. TScratch: A novel and simple software tool for automated analysis of monolayer wound healing assays. Biotechniques. 2009;46:265–274. doi: 10.2144/000113083. PubMed DOI

Zhang S, Yu D. Targeting Src family kinases in anti-cancer therapies: Turning promise into triumph. Trends Pharmacol Sci. 2012;33:122–128. doi: 10.1016/j.tips.2011.11.002. PubMed DOI PMC

Vanderlaag KE, Hudak S, Bald L, Fayadat-Dilman L, Sathe M, Grein J, Janatpour MJ. Anterior gradient-2 plays a critical role in breast cancer cell growth and survival by modulating cyclin D1, estrogen receptor-alpha and survivin. Breast Cancer Res. 2010;12:R32. doi: 10.1186/bcr2586. PubMed DOI PMC

Chen Y, Long H, Wu Z, Jiang X, Ma L. EGF transregulates opioid receptors through EGFR-mediated GRK2 phosphorylation and activation. Mol Biol Cell. 2008;19:2973–2983. doi: 10.1091/mbc.e07-10-1058. PubMed DOI PMC

Hrstka R, Nenutil R, Fourtouna A, Maslon MM, Naughton C, Langdon S, Murray E, Larionov A, Petrakova K, Muller P, et al. The pro-metastatic protein anterior gradient-2 predicts poor prognosis in tamoxifen-treated breast cancers. Oncogene. 2010;29:4838–4847. doi: 10.1038/onc.2010.228. PubMed DOI

Fritzsche FR, Dahl E, Pahl S, Burkhardt M, Luo J, Mayordomo E, Gansukh T, Dankof A, Knuechel R, Denkert C, et al. Prognostic relevance of AGR2 expression in breast cancer. Clin Cancer Res. 2006;12:1728–1734. doi: 10.1158/1078-0432.CCR-05-2057. PubMed DOI

Bu H, Bormann S, Schafer G, Horninger W, Massoner P, Neeb A, Lakshmanan VK, Maddalo D, Nestl A, Sültmann H, et al. The anterior gradient 2 (AGR2) gene is overexpressed in prostate cancer and may be useful as a urine sediment marker for prostate cancer detection. Prostate. 2011;71:575–587. doi: 10.1002/pros.21273. PubMed DOI

Ramachandran V, Arumugam T, Wang H, Logsdon CD. Anterior gradient 2 is expressed and secreted during the development of pancreatic cancer and promotes cancer cell survival. Cancer Res. 2008;68:7811–7818. doi: 10.1158/0008-5472.CAN-08-1320. PubMed DOI PMC

de Souza WF, Fortunato-Miranda N, Robbs BK, de Araujo WM, de-Freitas-Junior JC, Bastos LG, Viola JP, Morgado-Díaz JA. Claudin-3 overexpression increases the malignant potential of colorectal cancer cells: Roles of ERK1/2 and PI3K-Akt as modulators of EGFR signaling. PLoS One. 2013;8:e74994. doi: 10.1371/journal.pone.0074994. PubMed DOI PMC

Shao H, Gu Y, Ding J, Lu P, Ruan T, Lu W. HEPACAM inhibited the growth and migration of cancer cells in the progression of non-small cell lung cancer. Tumour Biol. 2016;37:2621–2627. doi: 10.1007/s13277-015-4084-9. PubMed DOI

Maurel M, Obacz J, Avril T, Ding YP, Papadodima O, Treton X, Daniel F, Pilalis E, Hörberg J, Hou W, et al. Control of anterior GRadient 2 (AGR2) dimerization links endoplasmic reticulum proteostasis to inflammation. EMBO Mol Med. 2019;11(pii):e10120. doi: 10.15252/emmm.201810120. PubMed DOI PMC

Aberger F, Weidinger G, Grunz H, Richter K. Anterior specification of embryonic ectoderm: The role of the Xenopus cement gland-specific gene XAG-2. Mech Dev. 1998;72:115–130. doi: 10.1016/S0925-4773(98)00021-5. PubMed DOI

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...