{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:12:27Z","timestamp":1789535547768,"version":"build-2803163510"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Current studies have shown that ARNTL, an important clock gene, plays an anticancer role and is downregulated in certain types of cancer. However, the biological functions and mechanisms of ARNTL in tumors remain largely unknown. This study aimed to elucidate how ARNTL\u2010induced autophagy impacts the biological properties of tongue squamous cell carcinoma (TSCC) cells and the mechanisms by which ARNTL expression activates autophagy. ARNTL was stably overexpressed in TSCC cells to investigate its functions in vitro and in vivo. We found that activation of autophagy induced by ARNTL decreases cell proliferation, enhances cell death, and hinders the migratory ability of TSCC cells. Moreover, ARNTL antagonizes the AKT\/mTOR pathway, which potentiates autophagy induction. The manipulation of Akt activation cancels the effects of ARNTL overexpression on the biological behaviors of TSCC cells. Furthermore, after the addition of SC79, the upregulated BAX expression due to ARNTL overexpression and downregulated expressions of BCL\u20102 and MMP2 were remarkably rescued. In vivo tumorigenicity assays and immunohistochemistry also confirmed that ARNTL overexpression suppresses tumor development. Our study found for the first time that ARNTL inhibits the malignant behaviors of oral cancer cells by regulating autophagy in an AKT\/mTOR pathway\u2010dependent manner, which provides a novel theoretical basis for the potential future application of ARNTL to treat patients with oral cancer.<\/jats:p>","DOI":"10.1111\/cas.15928","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T20:29:52Z","timestamp":1691699392000},"page":"3914-3923","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<scp>ARNTL<\/scp>\n                    inhibits the malignant behaviors of oral cancer by regulating autophagy in an\n                    <scp>AKT<\/scp>\n                    \/\n                    <scp>mTOR<\/scp>\n                    pathway\u2010dependent manner"],"prefix":"10.1111","volume":"114","author":[{"given":"KuiChi","family":"Chen","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences  Chongqing China"},{"name":"Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-9678","authenticated-orcid":false,"given":"HanXue","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences  Chongqing China"},{"name":"Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education  Chongqing China"},{"name":"Stomatological Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YueHeng","family":"Li","sequence":"additional","affiliation":[{"name":"Stomatological Hospital of Chongqing Medical University  Chongqing 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