{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:24:38Z","timestamp":1791815078296,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Tumour metabolic modulation represents a promising adjuvant therapeutic strategy for cancers, including colorectal cancer (CRC). Dapagliflozin, a clinically approved sodium\u2012glucose cotransporter 2 (SLC5A2\/SGLT2) inhibitor, has attracted considerable attention, yet its functional role in CRC remains unclear. Here, we investigated the oncogenic effect of SLC5A2 on the colorectal mucosal epithelium using transgenic rats and an azoxymethane\/dextran sulphate sodium (AOM\/DSS)\u2010induced tumour model. Multiple immunofluorescence and tissue microarray analyses of clinical samples revealed an inverse correlation between SLC5A2 expression and natural killer (NK) cell infiltration, highlighting the therapeutic potential of dapagliflozin for CRC treatment. Mechanistically, gene expression profiling analysis and coculture experiments demonstrated that SLC5A2 impairs NKG2D\u2010mediated NK cell cytotoxicity. Furthermore, perforated patch\u2012clamp and calcium imaging revealed that SLC5A2 modulates the membrane potential and calcium influx, enhancing MHC\u2010I\u2010associated MICA\/B secretion via extracellular vesicle (EV) formation and thereby enabling CRC cells to evade NK cell surveillance. Our findings reveal a critical oncogenic role of SLC5A2 in CRC progression and suggest dapagliflozin as a novel therapeutic option, particularly for CRC patients with metabolic comorbidities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70657","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:46:50Z","timestamp":1776059210000},"source":"Crossref","is-referenced-by-count":1,"title":["Targeting SLC5A2 suppresses colorectal tumour development by enhancing NK cell activity through extracellular vesicle\u2010dependent MICA\/B signalling"],"prefix":"10.1002","volume":"16","author":[{"given":"Jun","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Pathology Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Department of Urology The Fifth Affiliated Hospital of Southern Medical University  Guangzhou China"},{"name":"Department of Pathology &amp; Guangdong Province Key Laboratory of Molecular 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Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyan","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Pathology Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"Department of Pathology &amp; Guangdong Province Key Laboratory of Molecular Tumor Pathology, School of Basic Medical Science Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4263-8873","authenticated-orcid":false,"given":"Rui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology Nanfang Hospital 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