{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T06:44:33Z","timestamp":1768977873953,"version":"3.49.0"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000938","name":"Department of Veterans Affairs, Australian Government","doi-asserted-by":"publisher","award":["IO1 BX003456"],"award-info":[{"award-number":["IO1 BX003456"]}],"id":[{"id":"10.13039\/501100000938","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007921","name":"University of Pittsburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>TMEM16A, a Ca<jats:sup>2+<\/jats:sup>\u2010activated Cl<jats:sup>\u2212<\/jats:sup> channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR\/HER family\u2010targeting biological therapies. Inhibition of TMEM16A Cl<jats:sup>\u2212<\/jats:sup> channel activity in breast cancer cells with <jats:italic>HER2<\/jats:italic> amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl<jats:sup>\u2212<\/jats:sup> channel inhibition. Treatment of HNSCC cells with cetuximab, a monoclonal antibody targeting EGFR, and simultaneous TMEM16A suppression led to a pronounced loss of viability. Biochemical analyses of cells subjected to TMEM16A inhibitors or expressing chloride\u2010deficient forms of TMEM16A provide further evidence that TMEM16A channel function may play a role in regulating EGFR\/HER2 signaling. These data demonstrate that TMEM16A regulates EGFR and HER2 in growth and survival pathways. Furthermore, in the absence of TMEM16A cotargeting, tumor cells may acquire resistance to EGFR\/HER inhibitors. Finally, targeting TMEM16A improves response to biological therapies targeting EGFR\/HER family members.<\/jats:p>","DOI":"10.1002\/gcc.22450","type":"journal-article","created":{"date-parts":[[2017,2,8]],"date-time":"2017-02-08T16:02:40Z","timestamp":1486569760000},"page":"460-471","source":"Crossref","is-referenced-by-count":40,"title":["TMEM16A\/ANO1 suppression improves response to antibody\u2010mediated targeted therapy of EGFR and HER2\/ERBB2"],"prefix":"10.1002","volume":"56","author":[{"given":"Sucheta","family":"Kulkarni","sequence":"first","affiliation":[{"name":"Department of Otolaryngology University of Pittsburgh Medical Center Pittsburgh Pennsylvania"},{"name":"Veterans Affairs Pittsburgh Health System Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anke","family":"Bill","sequence":"additional","affiliation":[{"name":"Novartis Institute for Biomedical Research Cambridge MA 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