GALNT2 promotes invasiveness of colorectal cancer cells partly through AXL

Ying Yu Liao, Ya Ting Chuang, Hsuan Yu Lin, Neng Yu Lin, Tzu Wen Hsu, Szu Chia Hsieh, Syue Ting Chen, Ji Shiang Hung, Hung Jen Yang, Jin Tung Liang, Min Chuan Huang*, John Huang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

7 Scopus citations

Abstract

GalNAc-type O-glycosylation and its initiating GalNAc transferases (GALNTs) play crucial roles in a wide range of cellular behaviors. Among 20 GALNT members, GALNT2 is consistently associated with poor survival of patients with colorectal cancer in public databases. However, its clinicopathological significance in colorectal cancer remains unclear. In this study, immunohistochemistry showed that GALNT2 was overexpressed in colorectal tumors compared with the adjacent nontumor tissues. GALNT2 overexpression was associated with poor survival of colorectal cancer patients. Forced expression of GALNT2 promoted migration and invasion as well as peritoneal metastasis of colorectal cancer cells. In contrast, GALNT2 knockdown with siRNAs or knockout with CRISPR/Cas9 system suppressed these malignant properties. Interestingly, we found that GALNT2 modified O-glycans on AXL and determined AXL levels via the proteasome-dependent pathway. In addition, the GALNT2-promoted invasiveness was significantly reversed by AXL siRNAs. These findings suggest that GALNT2 promotes colorectal cancer invasion at least partly through AXL.

Original languageEnglish
Pages (from-to)119-133
Number of pages15
JournalMolecular Oncology
Volume17
Issue number1
DOIs
StatePublished - 01 2023

Bibliographical note

© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Keywords

  • AXL
  • GALNT
  • glycosylation
  • invasion
  • Neoplasm Invasiveness
  • Humans
  • Cell Line, Tumor
  • Colorectal Neoplasms/genetics
  • Glycosylation
  • Polypeptide N-acetylgalactosaminyltransferase
  • N-Acetylgalactosaminyltransferases/genetics

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