N-acetylgalactosaminyltransferase GALNT6 is a potential therapeutic target of clear cell renal cell carcinoma progression.
N‐acetylgalactosaminyltransferase 6
O‐glycosylation
clear cell renal cell carcinoma
metastasis
prohibitin 2
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
06 Aug 2024
06 Aug 2024
Historique:
revised:
04
07
2024
received:
07
04
2024
accepted:
15
07
2024
medline:
6
8
2024
pubmed:
6
8
2024
entrez:
6
8
2024
Statut:
aheadofprint
Résumé
High expression of truncated O-glycans 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-acetylgalactosaminyltransferases (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-mediated O-glycosylation aggravates malignant behaviors. Gain- and loss-of-function experiments showed that overexpression of GALNT6 accelerated ccRCC cell proliferation, migration, and invasion, as well as promoted ccRCC-derived 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-directed mutagenesis assays, we found that O-glycosylation of prohibitin 2 (PHB2) at Ser161 was required for the GALNT6-induced ccRCC cell proliferation, migration, and invasion. Additionally, we identified lens epithelium-derived 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-mediated abnormal O-glycosylation promotes ccRCC progression, which provides a potential therapeutic target in ccRCC development.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : High-quality Development Fund Project of Science and Technology of China Medical University
ID : 2023JH2/20200023
Informations de copyright
© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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