{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:33:37Z","timestamp":1777635217819,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>High expression of truncated O\u2010glycans Tn antigen predicts adverse clinical outcome in patients with clear cell renal cell carcinoma (ccRCC). To understand the biosynthetic underpinnings of Tn antigen changes in ccRCC, we focused on N\u2010acetylgalactosaminyltransferases (GALNTs, also known as GalNAcTs) known to be involved in Tn antigen synthesis. Data from GSE15641 profile and local cohort showed that GALNT6 was significantly upregulated in ccRCC tissues. The current study aimed to determine the role of GALNT6 in ccRCC, and whether GALNT6\u2010mediated O\u2010glycosylation aggravates malignant behaviors. Gain\u2010 and loss\u2010of\u2010function experiments showed that overexpression of GALNT6 accelerated ccRCC cell proliferation, migration, and invasion, as well as promoted ccRCC\u2010derived xenograft tumor growth and lung metastasis. In line with this, silencing of GALNT6 yielded the opposite results. Mechanically, high expression of GALNT6 led to the accumulation of Tn antigen in ccRCC cells. By undertaking immunoprecipitation coupled with liquid chromatography\/mass spectrometry, vicia villosa agglutinin blot, and site\u2010directed mutagenesis assays, we found that O\u2010glycosylation of prohibitin 2 (PHB2) at Ser161 was required for the GALNT6\u2010induced ccRCC cell proliferation, migration, and invasion. Additionally, we identified lens epithelium\u2010derived growth factor (LEDGF) as a key regulator of GALNT6 transcriptional induction in ccRCC growth and an upstream contributor to ccRCC aggressive behavior. Collectively, our findings indicate that GALNT6\u2010mediated abnormal O\u2010glycosylation promotes ccRCC progression, which provides a potential therapeutic target in ccRCC development.<\/jats:p>","DOI":"10.1111\/cas.16296","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T09:46:18Z","timestamp":1722937578000},"page":"3320-3332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["N\u2010acetylgalactosaminyltransferase GALNT6 is a potential therapeutic target of clear cell renal cell carcinoma progression"],"prefix":"10.1111","volume":"115","author":[{"given":"Luhaoran","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of China Medical University  Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery 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