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Recent studies have identified the secreted frizzled\u2010related protein 2 (SFRP2) as a key player in this malignancy, showing its overexpression in metastatic cases. This research aimed to elucidate the molecular mechanisms by which SFRP2 influences colon cancer progression. We employed in\u00a0vitro assays to assess the effects of SFRP2 on cell migration and invasion, revealing that SFRP2 significantly enhances these processes without affecting cell proliferation. Mechanistically, we found that SFRP2 interacts with Snai1, a transcription factor known to promote epithelial\u2010mesenchymal transition (EMT), thereby stabilizing Snai1 protein levels. Furthermore, SFRP2 was shown to inhibit Snai1 ubiquitination through the deubiquitinase USP11, leading to increased Snai1 activity. Notably, Snai1 also positively regulates SFRP2 transcription, establishing a feedback loop that amplifies their expression. Our findings indicate that the SFRP2\u2010Snai1 axis promotes colon cancer cell migration and invasion via the phosphoinositide 3\u2010kinase (PI3K)\/protein kinase B (AKT)\/mammalian target of rapamycin (mTOR) signalling pathway. In\u00a0vivo experiments further confirmed that the SFRP2\u2010Snai1 interaction significantly enhances metastatic potential. Collectively, these results suggest that targeting the SFRP2\u2010Snai1 signalling pathway may provide a novel therapeutic strategy for metastatic colon cancer.<\/jats:p>","DOI":"10.1111\/jcmm.71318","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:32:21Z","timestamp":1789133541000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>SFRP2<\/scp>\n                    Potentiates Metastasis of Colon Cancer by Enhancing Snai1 Protein Stability via\n                    <scp>USP11<\/scp>"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3635-6075","authenticated-orcid":false,"given":"Yanshen","family":"Kuang","sequence":"first","affiliation":[{"name":"Department of General Surgery The First Medical Centre, Chinese PLA General Hospital  Beijing 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