{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:30:32Z","timestamp":1787923832141,"version":"build-2784847793"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Epidemiological evidence confirms high-fat diet (HFD) as a key risk factor for colorectal cancer (CRC) progression. Aryl hydrocarbon receptor (AhR), a ligand-dependent nuclear transcription factor enriched in intestinal tissues, regulates intestinal metabolism and tumorigenesis. However, its role and mechanism in HFD-induced CRC progression remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here, we constructed a HFD-induced obese CRC tumor-bearing mouse model and a free fatty acid (FFA)-treated CRC cell model to investigate AhR function and mechanism underlying in HFD-related CRC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      We found that HFD significantly promoted CRC progression, accompanying with activation of AhR with upregulated level of kynurenine (KYN) synthesis-related enzymes and increased KYN levels in tumor tissue and peripheral blood. The specific inhibition of AhR alleviated tumor growth and metastasis in tumor-bearing mouse with HFD treatment.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , FFA treatment induced AhR activation with high level of KYN secretion, which enhanced CRC cell growth, invasion and epithelial-mesenchymal transition (EMT). Genetic knockdown of AhR reversed FFA-induced malignant phenotypes. Quantitative proteomic analysis identified that inositol polyphosphate 4-phosphatase type II (INPP4B) might be a potential target for AhR function. Mechanistically, activated AhR directly transcriptionally upregulated INPP4B to trigger AKT\/SGK3 pathway activation, and knockdown of INPP4B abolished AhR activation-induced oncogenic effects. In conclusion, AhR promotes HFD-related subcutaneous tumor growth and invasion\/migration-related phenotypes of CRC via activating the INPP4B\/AKT\/SGK3 pathway, which may provide a potential target for the prevention or treatment of HFD-associated CRC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1907461","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:51:01Z","timestamp":1787921461000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Aryl hydrocarbon receptor promotes the proliferation and aggressive progression of colorectal cancer under high-fat diet via activating INPP4B\/AKT\/SGK3 signaling pathway"],"prefix":"10.3389","volume":"16","author":[{"given":"Qiguan","family":"Dong","sequence":"first","affiliation":[{"name":"Graduate School of Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Department of 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, General Hospital of Fushun Mining Bureau of Liaoning Health Industry Group","place":["Fushun, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianzhi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, General Hospital of Fushun Mining Bureau of Liaoning Health Industry Group","place":["Fushun, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengjiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, General Hospital of Northern Theater Command","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, General 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