{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:21:45Z","timestamp":1785432105866,"version":"3.56.0"},"posted":{"date-parts":[[2025,8,26]]},"group-title":"Cancer Biology","reference-count":33,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["K08DK120871"],"award-info":[{"award-number":["K08DK120871"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30DK034854-36"],"award-info":[{"award-number":["P30DK034854-36"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Division of Newborn Medicine"],"award-info":[{"award-number":["Division of Newborn Medicine"]}],"id":[{"id":"https:\/\/ror.org\/00dvg7y05","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the United States, and upregulation of the WNT pathway is a primary driver in most cases. However, the role of individual WNT proteins in the development of CRC remains poorly understood. Our previous studies demonstrated that WNT2B loss-of-function leads to severe intestinal enteropathy in humans and increases chemically-induced colitis in mice, suggesting a protective function in the colon. Therefore, we investigated how loss of WNT2B affects CRC development. We used azoxymethane (AOM)\/dextran sodium sulfate (DSS) to model colitis-associated cancer (CAC) and AOM-induced mutagenesis to model sporadic CRC. We measured the number and size of tumors and performed histopathological and molecular analyses. We also analyzed the Cancer Genome Atlas to evaluate\n                  <jats:italic>WNT2B<\/jats:italic>\n                  expression in human colon cancer. In CAC and CRC mouse models,\n                  <jats:italic>Wnt2b KO<\/jats:italic>\n                  mice showed decreased survival and enhanced tumor burden. Moreover,\n                  <jats:italic>Wnt2b KO<\/jats:italic>\n                  mice had larger tumors and enhanced dysplasia, with a higher frequency of animals progressing from adenomas to adenocarcinomas compared to control littermates.\n                  <jats:italic>Wnt2b KO<\/jats:italic>\n                  animals frequently presented with intestinal bleeding and rectum prolapse, which resembles obstructive CRC. Furthermore,\n                  <jats:italic>WNT2B<\/jats:italic>\n                  expression was downregulated in human CRC samples compared to healthy controls, which predicted a significantly lower patient survival. These findings support the conclusion that WNT2B is required for maximal resistance against tumorigenesis and raise the possibility that selectively increasing WNT2B signaling may be a useful colon cancer prevention strategy.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>WNT2B loss-of-function increases colon cancer tumorigenesis. Targeting WNT2B may represent a novel strategy for intestinal diseases with a high risk of neoplastic transformation, potentially decreasing the progression to cancer development.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.08.21.671161","type":"posted-content","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T14:19:33Z","timestamp":1756217973000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of WNT2B Increases Progression from Dysplasia to Colorectal Cancer"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2681-6289","authenticated-orcid":false,"given":"Luiz Fernando","family":"Silva Oliveira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Syuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3151-4162","authenticated-orcid":false,"given":"Sathuwarman","family":"Raveenthiraraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaedeok","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkata Siva","family":"Dasuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9571-0344","authenticated-orcid":false,"given":"Comfort","family":"Adegboye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3487-4641","authenticated-orcid":false,"given":"Juan","family":"Putra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9435-275X","authenticated-orcid":false,"given":"Jorge O.","family":"Munera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-0189","authenticated-orcid":false,"given":"Diana L.","family":"Carlone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0402-4857","authenticated-orcid":false,"given":"David T.","family":"Breault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9298-6991","authenticated-orcid":false,"given":"Amy E.","family":"O\u2019Connell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025082908450710000_2025.08.21.671161v1.1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21772"},{"key":"2025082908450710000_2025.08.21.671161v1.2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"2025082908450710000_2025.08.21.671161v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nature11252"},{"key":"2025082908450710000_2025.08.21.671161v1.4","doi-asserted-by":"crossref","unstructured":"Oliveira LFS , Predes D , Borges HL , Abreu JG . 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