GALNT2 sustains glioma stem cells by promoting CD44 expression

Glioblastoma (GBM) is the most prevalent and malignant brain tumor and is highly resistant to currently available treatment. In this study, we reveal that polypeptide N-acetylgalactosaminyltransferase 5 (GALNT2) expression level was elevated in GBM, IDH1 wildtype glioma, and GBM stem cells (GSCs). GALNT2 increased expression correlated with GBM patients' unfavorable clinical outcomes. Functionally, targeting GALNT2 blocks GSCs cell proliferation, self-renewal, and malignant invasion through repressing CD44 expression. Most importantly, we first provide evidence suggesting that STAT3 activates GALNT2 expression at the transcriptional level by directly binding to the GALNT2 promoter. Through a rational screening, we found a GALNT2 inhibitor that dramatically suppresses GSCs self-maintenance in vitro and in vivo. Collectively, we uncovered the critical function of GALNT2 in promoting GSCs self-maintenance and GBM progression and may provide a new potential drug for GBM clinical therapy.

Automated summary

In this study, researchers found that the expression level of GALNT2 is elevated in GBM, IDH1 wildtype glioma, and GSCs. GALNT2 expression is correlated with unfavorable clinical outcomes in GBM patients. Targeting GALNT2 can block GSCs cell proliferation, self-renewal, and malignant invasion through repressing CD44 expression.