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Melatonin possesses significant anticarcinogenic activity. However, whether melatonin induces autophagy and its roles in cell death in\n TSCC<\/jats:styled-content>\n are unclear. Herein, we show that melatonin induced significant apoptosis in the\n TSCC<\/jats:styled-content>\n cell line Cal27. Apart from the induction of apoptosis, we demonstrated that melatonin\u2010induced autophagic flux in Cal27 cells as evidenced by the formation of\n GFP<\/jats:styled-content>\n \u2010\n LC<\/jats:styled-content>\n 3 puncta, and the upregulation of\n LC<\/jats:styled-content>\n 3\u2010\n II<\/jats:styled-content>\n and downregulation of\n SQSTM<\/jats:styled-content>\n 1\/P62. Moreover, pharmacological or genetic blockage of autophagy enhanced melatonin\u2010induced apoptosis, indicating a cytoprotective role of autophagy in melatonin\u2010treated Cal27 cells. Mechanistically, melatonin induced\n TFE<\/jats:styled-content>\n 3\n (Ser321)<\/jats:sup>\n dephosphorylation, subsequently activated\n TFE<\/jats:styled-content>\n 3 nuclear translocation, and increased\n TFE<\/jats:styled-content>\n 3 reporter activity, which contributed to the expression of autophagy\u2010related genes and lysosomal biogenesis. Luzindole, a melatonin membrane receptor blocker, or\n \n MT<\/jats:styled-content>\n 2\n <\/jats:italic>\n \u2010si\n RNA<\/jats:styled-content>\n partially blocked the ability of melatonin to promote\n mTORC<\/jats:styled-content>\n 1\/\n TFE<\/jats:styled-content>\n 3 signaling. Furthermore, we verified in a xenograft mouse model that melatonin with hydroxychloroquine or\n \n TFE<\/jats:styled-content>\n 3\n <\/jats:italic>\n \u2010si\n RNA<\/jats:styled-content>\n exerted a synergistic antitumor effect by inhibiting autophagy. Importantly,\n TFE<\/jats:styled-content>\n 3 expression positively correlated with\n TSCC<\/jats:styled-content>\n development and poor prognosis in patients. Collectively, we demonstrated that the melatonin\u2010induced increase in\n TFE<\/jats:styled-content>\n 3\u2010dependent autophagy is mediated through the melatonin membrane receptor in\n TSCC<\/jats:styled-content>\n . These data also suggest that blocking melatonin membrane receptor\u2010\n TFE<\/jats:styled-content>\n 3\u2010dependent autophagy to enhance the activity of melatonin warrants further attention as a treatment strategy for\n TSCC<\/jats:styled-content>\n .\n <\/jats:p>","DOI":"10.1111\/jpi.12457","type":"journal-article","created":{"date-parts":[[2017,11,17]],"date-time":"2017-11-17T09:36:39Z","timestamp":1510911399000},"source":"Crossref","is-referenced-by-count":74,"title":["RETRACTED: Inhibiting\n MT<\/scp>\n 2\u2010\n TFE<\/scp>\n 3\u2010dependent autophagy enhances melatonin\u2010induced apoptosis in tongue squamous cell carcinoma"],"prefix":"10.1111","volume":"64","author":[{"given":"Tengfei","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery The Second Xiangya Hospital of Central South University Changsha Hunan 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