The most common primary malignancy of the liver, hepatocellular carcinoma (HCC), is a heterogeneous tumor entity with high metastatic potential and complex pathophysiology. Increasing evidence suggests that tissue mechanics plays a critical role in tumor onset and progression. Here, we show that plectin, a major cytoskeletal crosslinker protein, plays a crucial role in mechanical homeostasis and mechanosensitive oncogenic signaling that drives hepatocarcinogenesis. Our expression analyses revealed elevated plectin levels in liver tumors, which correlated with poor prognosis for HCC patients. Using autochthonous and orthotopic mouse models we demonstrated that genetic and pharmacological inactivation of plectin potently suppressed the initiation and growth of HCC. Moreover, plectin targeting potently inhibited the invasion potential of human HCC cells and reduced their metastatic outgrowth in the lung. Proteomic and phosphoproteomic profiling linked plectin-dependent disruption of cytoskeletal networks to attenuation of oncogenic FAK, MAPK/Erk, and PI3K/Akt signatures. Importantly, by combining cell line-based and murine HCC models, we show that plectin inhibitor plecstatin-1 (PST) is well-tolerated and potently inhibits HCC progression. In conclusion, our study demonstrates that plectin-controlled cytoarchitecture is a key determinant of HCC development and suggests that pharmacologically induced disruption of mechanical homeostasis may represent a new therapeutic strategy for HCC treatment.

Department of Analytical Chemistry University of Vienna Vienna Austria

Department of Biochemistry and Cell Biology Max F Perutz Laboratories University of Vienna Vienna Austria

Department of Biology North Park University Chicago United States

Department of Cell Biology Faculty of Science Charles University BIOCEV Prumyslova Vestec Czech Republic

Department of Clinical and Transplant Pathology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of General and Visceral Surgery Ulm University Hospital Ulm Germany

Department of Natural Sciences Faculty of Biomedical Engineering Czech Technical University Prague Prague Czech Republic

Department of Pathology 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Physics University of Erlangen Nuremberg Erlangen Germany

Department of Radiodiagnostic and Interventional Radiology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Surgery University Hospital Mannheim Medical Faculty Mannheim University of Heidelberg Mannheim Germany

Division of Chronic Inflammation and Cancer German Cancer Research Center Im Neuenheimer Feld Heidelberg Germany

Institute of Inorganic Chemistry University of Vienna Vienna Austria

Institute of Molecular Cancer Research University of Zurich Zurich Switzerland

Joint Metabolome Facility Medical University of Vienna and University of Vienna Heidelberg Germany

Laboratory of Integrative Biology Institute of Molecular Genetics of the Czech Academy of Sciences Prague Czech Republic

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doi: 10.1101/2024.08.02.606331 PubMed

Před aktualizací

doi: 10.7554/eLife.102205.1 PubMed

Před aktualizací

doi: 10.7554/eLife.102205.2 PubMed

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Abrahamsberg C, Fuchs P, Osmanagic-Myers S, Fischer I, Propst F, Elbe-Bürger A, Wiche G. Targeted ablation of plectin isoform 1 uncovers role of cytolinker proteins in leukocyte recruitment. PNAS. 2005;102:18449–18454. doi: 10.1073/pnas.0505380102. PubMed DOI PMC

Ackerl R, Walko G, Fuchs P, Fischer I, Schmuth M, Wiche G. Conditional targeting of plectin in prenatal and adult mouse stratified epithelia causes keratinocyte fragility and lesional epidermal barrier defects. Journal of Cell Science. 2007;120:2435–2443. doi: 10.1242/jcs.004481. PubMed DOI

Andrä K, Nikolic B, Stöcher M, Drenckhahn D, Wiche G. Not just scaffolding: plectin regulates actin dynamics in cultured cells. Genes & Development. 1998;12:3442–3451. doi: 10.1101/gad.12.21.3442. PubMed DOI PMC

Bakewell SJ, Rangel DF, Ha DP, Sethuraman J, Crouse R, Hadley E, Costich TL, Zhou X, Nichols P, Lee AS. Suppression of stress induction of the 78-kilodalton glucose regulated protein (GRP78) in cancer by IT-139, an anti-tumor ruthenium small molecule inhibitor. Oncotarget. 2018;9:29698–29714. doi: 10.18632/oncotarget.25679. PubMed DOI PMC

Bhattacharya R, Gonzalez AM, Debiase PJ, Trejo HE, Goldman RD, Flitney FW, Jones JCR. Recruitment of vimentin to the cell surface by beta3 integrin and plectin mediates adhesion strength. Journal of Cell Science. 2009;122:1390–1400. doi: 10.1242/jcs.043042. PubMed DOI PMC

Bodor DL, Pönisch W, Endres RG, Paluch EK. Of cell shapes and motion: the physical basis of animal cell migration. Developmental Cell. 2020;52:550–562. doi: 10.1016/j.devcel.2020.02.013. PubMed DOI

Bouameur JE, Favre B, Borradori L. Plakins, a versatile family of cytolinkers: roles in skin integrity and in human diseases. The Journal of Investigative Dermatology. 2014;134:885–894. doi: 10.1038/jid.2013.498. PubMed DOI

Boyault S, Rickman DS, de Reyniès A, Balabaud C, Rebouissou S, Jeannot E, Hérault A, Saric J, Belghiti J, Franco D, Bioulac-Sage P, Laurent-Puig P, Zucman-Rossi J. Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets. Hepatology. 2007;45:42–52. doi: 10.1002/hep.21467. PubMed DOI

Broders-Bondon F, Nguyen Ho-Bouldoires TH, Fernandez-Sanchez ME, Farge E. Mechanotransduction in tumor progression: The dark side of the force. The Journal of Cell Biology. 2018;217:1571–1587. doi: 10.1083/jcb.201701039. PubMed DOI PMC

Buckup M, Rice MA, Hsu E-C, Garcia-Marques F, Liu S, Aslan M, Bermudez A, Huang J, Pitteri SJ, Stoyanova T. Plectin is a regulator of prostate cancer growth and metastasis. Oncogene. 2021;40:663–676. doi: 10.1038/s41388-020-01557-9. PubMed DOI PMC

Burch TC, Watson MT, Nyalwidhe JO. Variable metastatic potentials correlate with differential plectin and vimentin expression in syngeneic androgen independent prostate cancer cells. PLOS ONE. 2013;8:e65005. doi: 10.1371/journal.pone.0065005. PubMed DOI PMC

Burgstaller G, Gregor M, Winter L, Wiche G. Keeping the vimentin network under control: cell-matrix adhesion-associated plectin 1f affects cell shape and polarity of fibroblasts. Molecular Biology of the Cell. 2010;21:3362–3375. doi: 10.1091/mbc.E10-02-0094. PubMed DOI PMC

Burris HA, Bakewell S, Bendell JC, Infante J, Jones SF, Spigel DR, Weiss GJ, Ramanathan RK, Ogden A, Von Hoff D. Safety and activity of IT-139, a ruthenium-based compound, in patients with advanced solid tumours: a first-in-human, open-label, dose-escalation phase I study with expansion cohort. ESMO Open. 2016;1:e000154. doi: 10.1136/esmoopen-2016-000154. PubMed DOI PMC

Bustelo XR. RHO GTPases in cancer: known facts, open questions, and therapeutic challenges. Biochemical Society Transactions. 2018;46:741–760. doi: 10.1042/BST20170531. PubMed DOI PMC

Cappuyns S, Corbett V, Yarchoan M, Finn RS, Llovet JM. Critical appraisal of guideline recommendations on systemic therapies for advanced hepatocellular carcinoma: a review. JAMA Oncology. 2024;10:395–404. doi: 10.1001/jamaoncol.2023.2677. PubMed DOI PMC

Chiang DY, Villanueva A, Hoshida Y, Peix J, Newell P, Minguez B, LeBlanc AC, Donovan DJ, Thung SN, Solé M, Tovar V, Alsinet C, Ramos AH, Barretina J, Roayaie S, Schwartz M, Waxman S, Bruix J, Mazzaferro V, Ligon AH, Najfeld V, Friedman SL, Sellers WR, Meyerson M, Llovet JM. Focal gains of VEGFA and molecular classification of hepatocellular carcinoma. Cancer Research. 2008;68:6779–6788. doi: 10.1158/0008-5472.CAN-08-0742. PubMed DOI PMC

Cooper J, Giancotti FG. Integrin signaling in cancer: mechanotransduction, stemness, epithelial plasticity, and therapeutic resistance. Cancer Cell. 2019;35:347–367. doi: 10.1016/j.ccell.2019.01.007. PubMed DOI PMC

De Pascalis C, Pérez-González C, Seetharaman S, Boëda B, Vianay B, Burute M, Leduc C, Borghi N, Trepat X, Etienne-Manneville S. Intermediate filaments control collective migration by restricting traction forces and sustaining cell-cell contacts. The Journal of Cell Biology. 2018;217:3031–3044. doi: 10.1083/jcb.201801162. PubMed DOI PMC

Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, Zanconato F, Le Digabel J, Forcato M, Bicciato S, Elvassore N, Piccolo S. Role of YAP/TAZ in mechanotransduction. Nature. 2011;474:179–183. doi: 10.1038/nature10137. PubMed DOI

Eisenberg JL, Beaumont KG, Takawira D, Hopkinson SB, Mrksich M, Budinger GRS, Jones JCR. Plectin-containing, centrally localized focal adhesions exert traction forces in primary lung epithelial cells. Journal of Cell Science. 2013;126:3746–3755. doi: 10.1242/jcs.128975. PubMed DOI PMC

Esnault C, Stewart A, Gualdrini F, East P, Horswell S, Matthews N, Treisman R. Rho-actin signaling to the MRTF coactivators dominates the immediate transcriptional response to serum in fibroblasts. Genes & Development. 2014;28:943–958. doi: 10.1101/gad.239327.114. PubMed DOI PMC

Flocke LS, Trondl R, Jakupec MA, Keppler BK. Molecular mode of action of NKP-1339 - a clinically investigated ruthenium-based drug - involves ER- and ROS-related effects in colon carcinoma cell lines. Investigational New Drugs. 2016;34:261–268. doi: 10.1007/s10637-016-0337-8. PubMed DOI PMC

Flores IL, Kawahara R, Miguel MCC, Granato DC, Domingues RR, Macedo CCS, Carnielli CM, Yokoo S, Rodrigues PC, Monteiro BVB, Oliveira CE, Salmon CR, Nociti FH, Jr, Lopes MA, Santos-Silva A, Winck FV, Coletta RD, Paes Leme AF. EEF1D modulates proliferation and epithelial-mesenchymal transition in oral squamous cell carcinoma. Clinical Science. 2016;130:785–799. doi: 10.1042/CS20150646. PubMed DOI

Gregor M, Osmanagic-Myers S, Burgstaller G, Wolfram M, Fischer I, Walko G, Resch GP, Jörgl A, Herrmann H, Wiche G. Mechanosensing through focal adhesion-anchored intermediate filaments. FASEB Journal. 2014;28:715–729. doi: 10.1096/fj.13-231829. PubMed DOI

Gundesli H, Kori M, Arga KY. The versatility of plectin in cancer: a pan-cancer analysis on potential diagnostic and prognostic impacts of plectin isoforms. OMICS. 2023;27:281–296. doi: 10.1089/omi.2023.0053. PubMed DOI

Hoxhaj G, Manning BD. The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. Nature Reviews. Cancer. 2020;20:74–88. doi: 10.1038/s41568-019-0216-7. PubMed DOI PMC

Jirouskova M, Nepomucka K, Oyman-Eyrilmez G, Kalendova A, Havelkova H, Sarnova L, Chalupsky K, Schuster B, Benada O, Miksatkova P, Kuchar M, Fabian O, Sedlacek R, Wiche G, Gregor M. Plectin controls biliary tree architecture and stability in cholestasis. Journal of Hepatology. 2018;68:1006–1017. doi: 10.1016/j.jhep.2017.12.011. PubMed DOI

Jiu Y, Lehtimäki J, Tojkander S, Cheng F, Jäälinoja H, Liu X, Varjosalo M, Eriksson JE, Lappalainen P. Bidirectional interplay between vimentin intermediate filaments and contractile actin stress fibers. Cell Reports. 2015;11:1511–1518. doi: 10.1016/j.celrep.2015.05.008. PubMed DOI

Katada K, Tomonaga T, Satoh M, Matsushita K, Tonoike Y, Kodera Y, Hanazawa T, Nomura F, Okamoto Y. Plectin promotes migration and invasion of cancer cells and is a novel prognostic marker for head and neck squamous cell carcinoma. Journal of Proteomics. 2012;75:1803–1815. doi: 10.1016/j.jprot.2011.12.018. PubMed DOI

Ladd AD, Duarte S, Sahin I, Zarrinpar A. Mechanisms of drug resistance in HCC. Hepatology. 2024;79:926–940. doi: 10.1097/HEP.0000000000000237. PubMed DOI

Lee J-S, Chu I-S, Mikaelyan A, Calvisi DF, Heo J, Reddy JK, Thorgeirsson SS. Application of comparative functional genomics to identify best-fit mouse models to study human cancer. Nature Genetics. 2004;36:1306–1311. doi: 10.1038/ng1481. PubMed DOI

Liu Y-H, Ho C-C, Cheng C-C, Chao W-T, Pei R-J, Hsu Y-H, Lai Y-S. Cytokeratin 18-mediated disorganization of intermediate filaments is induced by degradation of plectin in human liver cells. Biochemical and Biophysical Research Communications. 2011;407:575–580. doi: 10.1016/j.bbrc.2011.03.066. PubMed DOI

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J-F, de Oliveira AC, Santoro A, Raoul J-L, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz J-F, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J, SHARP Investigators Study Group Sorafenib in advanced hepatocellular carcinoma. The New England Journal of Medicine. 2008;359:378–390. doi: 10.1056/NEJMoa0708857. PubMed DOI

Llovet JM, Montal R, Sia D, Finn RS. Molecular therapies and precision medicine for hepatocellular carcinoma. Nature Reviews. Clinical Oncology. 2018;15:599–616. doi: 10.1038/s41571-018-0073-4. PubMed DOI

Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, Lencioni R, Koike K, Zucman-Rossi J, Finn RS. Hepatocellular carcinoma. Nature Reviews. Disease Primers. 2021;7:2403. doi: 10.1038/s41572-020-00240-3. PubMed DOI

Marks PC, Hewitt BR, Baird MA, Wiche G, Petrie RJ. Plectin linkages are mechanosensitive and required for the nuclear piston mechanism of three-dimensional cell migration. Molecular Biology of the Cell. 2022;33:ar104. doi: 10.1091/mbc.E21-08-0414. PubMed DOI PMC

McInroy L, Määttä A. Plectin regulates invasiveness of SW480 colon carcinoma cells and is targeted to podosome-like adhesions in an isoform-specific manner. Experimental Cell Research. 2011;317:2468–2478. doi: 10.1016/j.yexcr.2011.07.013. PubMed DOI

Meier SM, Kreutz D, Winter L, Klose MHM, Cseh K, Weiss T, Bileck A, Alte B, Mader JC, Jana S, Chatterjee A, Bhattacharyya A, Hejl M, Jakupec MA, Heffeter P, Berger W, Hartinger CG, Keppler BK, Wiche G, Gerner C. An organoruthenium anticancer agent shows unexpected target selectivity for plectin. Angewandte Chemie. 2017;56:8267–8271. doi: 10.1002/anie.201702242. PubMed DOI

Meier-Menches SM, Zappe K, Bileck A, Kreutz D, Tahir A, Cichna-Markl M, Gerner C. Time-dependent shotgun proteomics revealed distinct effects of an organoruthenium prodrug and its activation product on colon carcinoma cells. Metallomics. 2019;11:118–127. doi: 10.1039/c8mt00152a. PubMed DOI

Moon SH, Huang CH, Houlihan SL, Regunath K, Freed-Pastor WA, Morris JP, Tschaharganeh DF, Kastenhuber ER, Barsotti AM, Culp-Hill R, Xue W, Ho YJ, Baslan T, Li X, Mayle A, de Stanchina E, Zender L, Tong DR, D’Alessandro A, Lowe SW, Prives C. p53 Represses the mevalonate pathway to mediate tumor suppression. Cell. 2019;176:564–580. doi: 10.1016/j.cell.2018.11.011. PubMed DOI PMC

Na S, Chowdhury F, Tay B, Ouyang M, Gregor M, Wang Y, Wiche G, Wang N. Plectin contributes to mechanical properties of living cells. American Journal of Physiology. Cell Physiology. 2009;296:C868–C77. doi: 10.1152/ajpcell.00604.2008. PubMed DOI PMC

Nikolic B, Mac Nulty E, Mir B, Wiche G. Basic amino acid residue cluster within nuclear targeting sequence motif is essential for cytoplasmic plectin-vimentin network junctions. The Journal of Cell Biology. 1996;134:1455–1467. doi: 10.1083/jcb.134.6.1455. PubMed DOI PMC

Osmanagic-Myers S, Rus S, Wolfram M, Brunner D, Goldmann WH, Bonakdar N, Fischer I, Reipert S, Zuzuarregui A, Walko G, Wiche G. Plectin reinforces vascular integrity by mediating crosstalk between the vimentin and the actin networks. Journal of Cell Science. 2015;128:4138–4150. doi: 10.1242/jcs.172056. PubMed DOI PMC

Pal K, Al-Suraih F, Gonzalez-Rodriguez R, Dutta SK, Wang E, Kwak HS, Caulfield TR, Coffer JL, Bhattacharya S. Multifaceted peptide assisted one-pot synthesis of gold nanoparticles for plectin-1 targeted gemcitabine delivery in pancreatic cancer. Nanoscale. 2017;9:15622–15634. doi: 10.1039/c7nr03172f. PubMed DOI PMC

Paumard-Hernández B, Calvete O, Inglada Pérez L, Tejero H, Al-Shahrour F, Pita G, Barroso A, Carlos Triviño J, Urioste M, Valverde C, González Billalabeitia E, Quiroga V, Francisco Rodríguez Moreno J, Fernández Aramburo A, López C, Maroto P, Sastre J, José Juan Fita M, Duran I, Lorenzo-Lorenzo I, Iranzo P, García Del Muro X, Ros S, Zambrana F, María Autran A, Benítez J. Whole exome sequencing identifies PLEC, EXO5 and DNAH7 as novel susceptibility genes in testicular cancer. International Journal of Cancer. 2018;143:1954–1962. doi: 10.1002/ijc.31604. PubMed DOI

Perez SM, Brinton LT, Kelly KA. Plectin in cancer: from biomarker to therapeutic target. Cells. 2021a;10:2246. doi: 10.3390/cells10092246. PubMed DOI PMC

Perez SM, Dimastromatteo J, Landen CN, Kelly KA. A Novel monoclonal antibody targeting cancer-specific plectin has potent antitumor activity in ovarian cancer. Cells. 2021b;10:2218. doi: 10.3390/cells10092218. PubMed DOI PMC

Perez-Riverol Y, Bandla C, Kundu DJ, Kamatchinathan S, Bai J, Hewapathirana S, John NS, Prakash A, Walzer M, Wang S, Vizcaíno JA. The PRIDE database at 20 years: 2025 update. Nucleic Acids Research. 2025;53:D543–D553. doi: 10.1093/nar/gkae1011. PubMed DOI PMC

Piersma B, Hayward MK, Weaver VM. Fibrosis and cancer: A strained relationship. Biochimica et Biophysica Acta. Reviews on Cancer. 2020;1873:188356. doi: 10.1016/j.bbcan.2020.188356. PubMed DOI PMC

Prechova M, Adamova Z, Schweizer A-L, Maninova M, Bauer A, Kah D, Meier-Menches SM, Wiche G, Fabry B, Gregor M. Plectin-mediated cytoskeletal crosstalk controls cell tension and cohesion in epithelial sheets. The Journal of Cell Biology. 2022;221:e202105146. doi: 10.1083/jcb.202105146. PubMed DOI PMC

Prechova M, Korelova K, Gregor M. Plectin. Current Biology: CB. 2023;33:R128–R130. doi: 10.1016/j.cub.2022.12.061. PubMed DOI

Revia S, Seretny A, Wendler L, Banito A, Eckert C, Breuer K, Mayakonda A, Lutsik P, Evert M, Ribback S, Gallage S, Chikh Bakri I, Breuhahn K, Schirmacher P, Heinrich S, Gaida MM, Heikenwälder M, Calvisi DF, Plass C, Lowe SW, Tschaharganeh DF. Histone H3K27 demethylase KDM6A is an epigenetic gatekeeper of mTORC1 signalling in cancer. Gut. 2022;71:1613–1628. doi: 10.1136/gutjnl-2021-325405. PubMed DOI PMC

Singal AG, Llovet JM, Yarchoan M, Mehta N, Heimbach JK, Dawson LA, Jou JH, Kulik LM, Agopian VG, Marrero JA, Mendiratta-Lala M, Brown DB, Rilling WS, Goyal L, Wei AC, Taddei TH. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78:1922–1965. doi: 10.1097/HEP.0000000000000466. PubMed DOI PMC

Strouhalova K, Přechová M, Gandalovičová A, Brábek J, Gregor M, Rosel D. Vimentin intermediate filaments as potential target for cancer treatment. Cancers. 2020;12:184. doi: 10.3390/cancers12010184. PubMed DOI PMC

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. PNAS. 2005;102:15545–15550. doi: 10.1073/pnas.0506580102. PubMed DOI PMC

Sun Z, Guo SS, Fässler R. Integrin-mediated mechanotransduction. The Journal of Cell Biology. 2016;215:445–456. doi: 10.1083/jcb.201609037. PubMed DOI PMC

Sutoh Yoneyama M, Hatakeyama S, Habuchi T, Inoue T, Nakamura T, Funyu T, Wiche G, Ohyama C, Tsuboi S. Vimentin intermediate filament and plectin provide a scaffold for invadopodia, facilitating cancer cell invasion and extravasation for metastasis. European Journal of Cell Biology. 2014;93:157–169. doi: 10.1016/j.ejcb.2014.03.002. PubMed DOI

Tolba R, Kraus T, Liedtke C, Schwarz M, Weiskirchen R. Diethylnitrosamine (DEN)-induced carcinogenic liver injury in mice. Laboratory Animals. 2015;49:59–69. doi: 10.1177/0023677215570086. PubMed DOI

Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z, Edfors F, Sanli K, von Feilitzen K, Oksvold P, Lundberg E, Hober S, Nilsson P, Mattsson J, Schwenk JM, Brunnström H, Glimelius B, Sjöblom T, Edqvist P-H, Djureinovic D, Micke P, Lindskog C, Mardinoglu A, Ponten F. A pathology atlas of the human cancer transcriptome. Science. 2017;357:eaan2507. doi: 10.1126/science.aan2507. PubMed DOI

Vahidnezhad H, Youssefian L, Harvey N, Tavasoli AR, Saeidian AH, Sotoudeh S, Varghaei A, Mahmoudi H, Mansouri P, Mozafari N, Zargari O, Zeinali S, Uitto J. Mutation update: The spectra of PLEC sequence variants and related plectinopathies. Human Mutation. 2022;43:1706–1731. doi: 10.1002/humu.24434. PubMed DOI PMC

Wang W, Zuidema A, Te Molder L, Nahidiazar L, Hoekman L, Schmidt T, Coppola S, Sonnenberg A. Hemidesmosomes modulate force generation via focal adhesions. The Journal of Cell Biology. 2020;219:e201904137. doi: 10.1083/jcb.201904137. PubMed DOI PMC

Wenta T, Schmidt A, Zhang Q, Devarajan R, Singh P, Yang X, Ahtikoski A, Vaarala M, Wei G-H, Manninen A. Disassembly of α6β4-mediated hemidesmosomal adhesions promotes tumorigenesis in PTEN-negative prostate cancer by targeting plectin to focal adhesions. Oncogene. 2022;41:3804–3820. doi: 10.1038/s41388-022-02389-5. PubMed DOI PMC

Wernitznig D, Meier-Menches SM, Cseh K, Theiner S, Wenisch D, Schweikert A, Jakupec MA, Koellensperger G, Wernitznig A, Sommergruber W, Keppler BK. Plecstatin-1 induces an immunogenic cell death signature in colorectal tumour spheroids. Metallomics. 2020;12:2121–2133. doi: 10.1039/d0mt00227e. PubMed DOI

Xu R, He S, Ma D, Liang R, Luo Q, Song G. Plectin downregulation inhibits migration and suppresses epithelial mesenchymal transformation of hepatocellular carcinoma cells via ERK1/2 signaling. International Journal of Molecular Sciences. 2022;24:73. doi: 10.3390/ijms24010073. PubMed DOI PMC

Yang Z, Zhang Y, Wang X, Huang J, Guo W, Wei P, Li G, Wang Z, Huang Z, Zhang L. Putative biomarkers of malignant transformation of sinonasal inverted papilloma into squamous cell carcinoma. The Journal of International Medical Research. 2019;47:2371–2380. doi: 10.1177/0300060519838385. PubMed DOI PMC

Yau T, Chan P, Epstein R, Poon RT. Evolution of systemic therapy of advanced hepatocellular carcinoma. World Journal of Gastroenterology. 2008;14:6437–6441. doi: 10.3748/wjg.14.6437. PubMed DOI PMC

Yau T, Hsu C, Kim TY, Choo SP, Kang YK, Hou MM, Numata K, Yeo W, Chopra A, Ikeda M, Kuromatsu R, Moriguchi M, Chao Y, Zhao H, Anderson J, Cruz CD, Kudo M. Nivolumab in advanced hepatocellular carcinoma: Sorafenib-experienced Asian cohort analysis. Journal of Hepatology. 2019;71:543–552. doi: 10.1016/j.jhep.2019.05.014. PubMed DOI

Yin X, Kong L, Liu P. Identification of prognosis-related molecular subgroups based on DNA methylation in pancreatic cancer. Clinical Epigenetics. 2021;13:109. doi: 10.1186/s13148-021-01090-w. PubMed DOI PMC

Yolland L, Burki M, Marcotti S, Luchici A, Kenny FN, Davis JR, Serna-Morales E, Müller J, Sixt M, Davidson A, Wood W, Schumacher LJ, Endres RG, Miodownik M, Stramer BM. Persistent and polarized global actin flow is essential for directionality during cell migration. Nature Cell Biology. 2019;21:1370–1381. doi: 10.1038/s41556-019-0411-5. PubMed DOI PMC

Zrelski MM, Hösele S, Kustermann M, Fichtinger P, Kah D, Athanasiou I, Esser PR, Wagner A, Herzog R, Kratochwill K, Goldmann WH, Kiritsi D, Winter L. Plectin deficiency in fibroblasts deranges intermediate filament and organelle morphology, migration, and adhesion. The Journal of Investigative Dermatology. 2024;144:547–562. doi: 10.1016/j.jid.2023.08.020. PubMed DOI

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GEO
GSE14520, GSE76427, GSE36376, GSE63898, GSE64041, GSE76297, GSE16757, GSE17856, GSE65485, GSE50579