{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:02:23Z","timestamp":1785301343075,"version":"3.55.0"},"reference-count":84,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Cancer stem cell (CSC) persistence drives recurrence and therapy resistance in oral squamous cell carcinoma (OSCC), but what keeps cells locked in this stem-like state is poorly understood. In this narrative review, we propose that CSC state is sustained not by any single pathway but by joint dysregulation of three interacting cell-biological systems: membrane potential (Vmem), communication between neighbouring cells through gap junctional intercellular communication (GJIC), and the Hippo\u2013YAP pathway. We argue that these systems act together on one common point\u2014the YAP protein, retained in the nucleus\u2014which switches on a SOX2-centred stemness gene programme and stabilises a self-reinforcing CSC state. Drawing on evidence from cancer genomics, developmental bioelectricity, connexin biology, and OSCC-specific studies, we reconstruct how membrane depolarisation, loss of gap junction coupling, FAT1 mutation, and Hippo pathway inactivation could converge on persistent nuclear YAP, and how betel quid\u2014the principal risk factor across South and Southeast Asia\u2014may engage all three systems at once. Because the model holds that each input reinforces the others, it predicts that targeting several together should displace CSC state more durably than targeting any one alone. We set out the testable predictions this framework generates.<\/jats:p>","DOI":"10.3390\/ijms27156649","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"6649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Convergence Model of Bioelectric, Gap Junctional, and Hippo\u2013YAP Signalling in Oral Cancer Stem Cell Maintenance"],"prefix":"10.3390","volume":"27","author":[{"given":"Surendra Kumar","family":"Acharya","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4354-3518","authenticated-orcid":false,"given":"Wei Cheong","family":"Ngeow","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-7462","authenticated-orcid":false,"given":"Firdaus","family":"Hariri","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Clinical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9165-2343","authenticated-orcid":false,"given":"Fong Fong","family":"Liew","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University of Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-3435","authenticated-orcid":false,"given":"Yee Fan","family":"Choon","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Faculty of Dental Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","first-page":"7","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. 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