{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T15:27:13Z","timestamp":1782660433532,"version":"3.54.5"},"reference-count":64,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R15DK109484"],"award-info":[{"award-number":["R15DK109484"]}]},{"name":"National Institutes of Health","award":["R03CA249473"],"award-info":[{"award-number":["R03CA249473"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>GPR4 is a proton-sensing G protein-coupled receptor highly expressed in vascular endothelial cells and has been shown to potentiate intestinal inflammation in murine colitis models. Herein, we evaluated the proinflammatory role of GPR4 in the development of colitis-associated colorectal cancer (CAC) using the dextran sulfate sodium (DSS) and azoxymethane (AOM) mouse models in wild-type and GPR4 knockout mice. We found that GPR4 contributed to chronic intestinal inflammation and heightened DSS\/AOM-induced intestinal tumor burden. Tumor blood vessel density was markedly reduced in mice deficient in GPR4, which correlated with increased tumor necrosis and reduced tumor cell proliferation. These data demonstrate that GPR4 ablation alleviates intestinal inflammation and reduces tumor angiogenesis, development, and progression in the AOM\/DSS mouse model.<\/jats:p>","DOI":"10.3390\/cancers15204974","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T10:04:39Z","timestamp":1697191479000},"page":"4974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["GPR4 Knockout Attenuates Intestinal Inflammation and Forestalls the Development of Colitis-Associated Colorectal Cancer in Murine Models"],"prefix":"10.3390","volume":"15","author":[{"given":"Mona A.","family":"Marie","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-6072","authenticated-orcid":false,"given":"Edward J.","family":"Sanderlin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander P.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie D.","family":"Cashwell","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Satturwar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"},{"name":"Department of Pathology, Wake Forest University, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8654-4927","authenticated-orcid":false,"given":"Li V.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1093\/ecco-jcc\/jjab102","article-title":"Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational Risks from Mechanisms to Medicines","volume":"15","author":"Porter","year":"2021","journal-title":"J. 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