TMEM16A inhibits autophagy and promotes the invasion of hypopharyngeal squamous cell carcinoma through mTOR pathway.

Autor:	Yang X; Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong Province, China.; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong Province, China., Cui L; Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong Province, China.; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong Province, China., Liu Z; Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong Province, China.; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong Province, China., Li Y; Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong Province, China.; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong Province, China., Wu X; Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong Province, China.; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong Province, China., Tian R; Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong Province, China.; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong Province, China., Jia C; Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong Province, China.; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong Province, China., Ren C; Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong Province, China.; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.; Shandong Provincial Innovation and Practice Base for Postdoctors, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China., Mou Y; Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong Province, China.; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong Province, China., Song X; Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong Province, China.; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.; Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong Province, China.
Jazyk:	angličtina
Zdroj:	Carcinogenesis [Carcinogenesis] 2024 Aug 12; Vol. 45 (8), pp. 569-581.
DOI:	10.1093/carcin/bgae020
Abstrakt:	Previous studies have indicated that transmembrane protein 16A (TMEM16A) plays a crucial role in the pathogenesis and progression of various tumors by influencing multiple signaling pathways. However, the role of TMEM16A in regulating autophagy via the mammalian target of rapamycin (mTOR) pathway and its impact on the development of hypopharyngeal squamous cell carcinoma (HSCC) remain unclear. Immunohistochemistry and western blotting were used to assess the expression of TMEM16A in HSCC tissues and metastatic lymph nodes. Manipulation of TMEM16A expression levels was achieved in the FaDu cell line through overexpression or knockdown, followed by assessment of its biological effects using cell colony formation, wound healing, transwell and invasion assays. Additionally, apoptosis and autophagy-related proteins, as well as autophagosome formation, were evaluated through western blotting, transmission electron microscopy and immunofluorescence following TMEM16A knockdown or overexpression in FaDu cells. Our study revealed significantly elevated levels of TMEM16A in both HSCC tissues and metastatic lymph nodes compared with normal tissues. In vitro experiments demonstrated that silencing TMEM16A led to a notable suppression of HSCC cell proliferation, invasion and migration. Furthermore, TMEM16A silencing effectively inhibited tumor growth in xenografted mice. Subsequent investigations indicated that knockdown of TMEM16A in HSCC cells could suppress mTOR activation, thereby triggering autophagic cell death by upregulating sequestosome-1 (SQSTM1/P62) and microtubule-associated protein light chain 3 II (LC3II). This study highlights the crucial role of TMEM16A in modulating autophagy in HSCC, suggesting its potential as a therapeutic target for the treatment of this malignancy. (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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