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MZF1, linked to leukemogenesis, has an unclear role in colon cancer. This study examined its function in colon tumorigenesis and signaling\u2010targeted therapies. Multi\u2010omics (RNA\u2010seq, CUT&amp;Tag) identified MZF1 targets, validated in vitro\/in vivo using xenografts and epithelial\u2010specific MZF1 knockout mice. Virtual screening found MZF1 inhibitors. MZF1 activated SnoN transcription, suppressing TGF\u2010\u03b2\/SMAD signaling. Overexpression enhanced proliferation and colony formation; knockdown reversed these. In vivo, MZF1\u2010overexpressing xenografts grew faster with more Ki67+ cells, while MZF1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice had reduced tumor burden. Organoids from MZF1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice grew poorly. 10Panx Acetate, an MZF1 inhibitor, disrupted MZF1\u2010SnoN interaction, inhibiting cell and xenograft growth. Our results indicate MZF1 as a key colon cancer regulator via SnoN\u2010mediated TGF\u2010\u03b2 pathway suppression and suggest 10Panx Acetate for precision therapy. MZF1\/SnoN co\u2010expression may predict aggressive disease.\n                  <\/jats:p>","DOI":"10.1002\/advs.77277","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:35:12Z","timestamp":1792557312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MZF1 Inhibits TGF\u03b2\u20101\/SMAD Signaling by Transcriptionally Activating SnoN to Augment Tumorigenic Potential in Colon Cancer"],"prefix":"10.1002","author":[{"given":"Siqi","family":"Sheng","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Medical School Affiliated Jinling Hospital Nanjing University  Nanjing Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9274-6023","authenticated-orcid":false,"given":"Mengxi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Medical School 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