{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:55:14Z","timestamp":1774936514903,"version":"3.50.1"},"reference-count":30,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Collaboration Program Grant","award":["2018"],"award-info":[{"award-number":["2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malignant pleural mesothelioma (MPM) is an aggressive malignancy with limited effective treatment options. Focal adhesion kinase (FAK) inhibitors have been shown to efficiently suppress MPM cell growth initially, with limited utility in the current clinical setting. In this study, we utilised a large collection of MPM cell lines and MPM tissue samples to study the role of E-cadherin (CDH1) and microRNA on the efficacy of FAK inhibitors in MPM. The immunohistochemistry (IHC) results showed that the majority of MPM FFPE samples exhibited either the absence of, or very low, E-cadherin protein expression in MPM tissue. We showed that MPM cells with high CDH1 mRNA levels exhibited resistance to the FAK inhibitor PND-1186. In summary, MPM cells that did not express CDH1 mRNA were sensitive to PND-1186, and MPM cells that retained CDH1 mRNA were resistant. A cell cycle analysis showed that PND-1186 induced cell cycle disruption by inducing the G2\/M arrest of MPM cells. A protein\u2212protein interaction study showed that EGFR is linked to the FAK pathway, and a target scan of the microRNAs revealed that microRNAs (miR-17, miR221, miR-222, miR137, and miR148) interact with EGFR 3\u2032UTR. Transfection of MPM cells with these microRNAs sensitised the CHD1-expressing FAK-inhibitor-resistant MPM cells to the FAK inhibitor.<\/jats:p>","DOI":"10.3390\/ijms221910225","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T09:59:15Z","timestamp":1632391155000},"page":"10225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Role of E-Cadherin and microRNA on FAK Inhibitor Response in Malignant Pleural Mesothelioma (MPM)"],"prefix":"10.3390","volume":"22","author":[{"given":"Man Lee","family":"Yuen","sequence":"first","affiliation":[{"name":"Asbestos Diseases Research Institute, Sydney, NSW 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Asbestos Diseases Research Institute, Sydney, NSW 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8430-5236","authenticated-orcid":false,"given":"Emma M.","family":"Rath","sequence":"additional","affiliation":[{"name":"Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia"},{"name":"School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takun","family":"Yu","sequence":"additional","affiliation":[{"name":"Asbestos Diseases Research Institute, Sydney, NSW 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Johnson","sequence":"additional","affiliation":[{"name":"Asbestos Diseases Research Institute, Sydney, NSW 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kadir Harun","family":"Sarun","sequence":"additional","affiliation":[{"name":"Asbestos Diseases Research Institute, Sydney, NSW 2139, Australia"},{"name":"NSW Health, Sydney, NSW 2065, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Provincial Engineering Research Centre of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"Concord Clinical School, The University of Sydney, Concord West, NSW 2138, Australia"},{"name":"Faculty of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Kao","sequence":"additional","affiliation":[{"name":"Asbestos Diseases Research Institute, Sydney, NSW 2139, Australia"},{"name":"Sydney Medical School, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Linton","sequence":"additional","affiliation":[{"name":"Asbestos Diseases Research Institute, Sydney, NSW 2139, Australia"},{"name":"Sydney Medical School, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candice Julie","family":"Clarke","sequence":"additional","affiliation":[{"name":"Anatomical Pathology Department, NSW Health Pathology, Concord Repatriation General Hospital, Concord, NSW 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian C.","family":"McCaughan","sequence":"additional","affiliation":[{"name":"Sydney Cardiothoracic Surgeons, RPA Medical Centre, Sydney, NSW 2042, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7310-2257","authenticated-orcid":false,"given":"Ken","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Asbestos Diseases Research Institute, Sydney, NSW 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Lee","sequence":"additional","affiliation":[{"name":"Asbestos Diseases Research Institute, Sydney, NSW 2139, Australia"},{"name":"Sydney Medical School, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Anatomical Pathology Department, NSW Health Pathology, Concord Repatriation General Hospital, Concord, NSW 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuen Yee","family":"Cheng","sequence":"additional","affiliation":[{"name":"Asbestos Diseases Research Institute, Sydney, NSW 2139, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/S0140-6736(15)01238-6","article-title":"Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed 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