TMEM16A Inhibits Autophagy and Promotes the Invasion of Hypopharyngeal Squamous Cell Carcinoma Through mTOR Pathway

Background: Previous investigations indicated that transmembrane protein 16A (TMEM16A) mediates the pathogenesis and malignant of many tumors through regulating multiple pathways. However, whether TMEM16A could regulate autophagy via mammalian target of rapamycin (mTOR) pathway to modulate hypopharyngeal squamous cell carcinoma (HSCC) occurrence and development or not is still unclear. Methods The expression of TMEM16A in HSCC and metastatic lymph nodes was detected by immunohistochemistry and western blot. TMEM16A was overexpressed or knocked down in FaDu cell line to evaluate its effects on the biological function by cell colony formation experiment, wound healing assay, trans well assay, and invasion assay. TMEM16A was knocked down or over expression in FaDu cells to test apoptosis and autophagy related protein and autophagosome formation by western blot, transmission electron microscopy and immunofluorescence. Results In the present study, we observe that the expression level of TMEM16A in HSCC and metastatic lymph nodes are significantly higher than that in normal tissues. The results of in-vitro experiments showed that silencing TMEM16A significantly inhibited the proliferation, invasion and migration of HSCC cells. Silencing TMEM16A inhibited tumor formation in xenografted mice. Further experiments demonstrated that knocking down TMEM16A in HSCC cells could block the activation of mTOR, and thus promote the initiation of the autophagic death by activating sequestosome-1 (SQSTM1/P62) and protein light chain 3II (LC3II). Conclusion Therefore, TMEM16A displays an important effect on autophagy in HSCC, which may provide a potential therapeutic target for the treatment of HSCC.