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Our aim was to elucidate the function of MTHFD1 in colorectal cancer (CRC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In vitro assessments of the proliferation, invasion, and migration abilities of CRC cells were conducted using Immunohistochemistry, Transwell invasion assays, Western blot (WB), and Cell counting Kit\u20108 assays. WB was also utilized to measure autophagy protein levels and PI3K\u2010AKT\u2010mTOR signaling pathway expression. Furthermore, the role of MTHFD1 was evaluated in\u00a0vivo by using subcutaneous xenograft tumor models and lateral tail vein metastasis models of human CRC in nude mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overexpression of MTHFD1 promoted the abilities of tumorigenesis and metastasis in CRC in\u00a0vitro and in\u00a0vivo and reduced autophagy, attributing to the PI3K\u2010AKT\u2010mTOR signaling pathway in CRC cells. In contrast, the down\u2010regulation of MTHFD1 increased autophagy and suppressed their proliferation, migration, and invasion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>MTHFD1 can modulate the PI3K\u2010AKT\u2010mTOR signaling pathway to suppress autophagy and stimulate tumorigenesis and metastasis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70267","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T23:46:32Z","timestamp":1732232792000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<scp>MTHFD1<\/scp> Regulates Autophagy to Promote Growth and Metastasis in Colorectal Cancer via the <scp>PI3K<\/scp>\u2010<scp>AKT<\/scp>\u2013<scp>mTOR<\/scp> Signaling Pathway"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-7994","authenticated-orcid":false,"given":"Zhihao","family":"Li","sequence":"first","affiliation":[{"name":"Department of General Surgery The Sixth Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Department of General Surgery Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoxian","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Sixth Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Department of General Surgery Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou Guangdong 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