GALNT6, GALNT14, and Gal-3 in association with GDF-15 promotes drug resistance and stemness of breast cancer via β-catenin axis

Growth Factors. 2024 May;42(2):84-100. doi: 10.1080/08977194.2024.2368907. Epub 2024 Jun 18.

Abstract

N-acetylgalactosaminyltransferases (GALNTs) are a polypeptide responsible for aberrant glycosylation in breast cancer (BC), but the mechanism is unclear. In this study, expression levels of GALNT6, GALNT14, and Gal-3 were assessed in BC, and their association with GDF-15, β-catenin, stemness (SOX2 and OCT4), and drug resistance marker (ABCC5) was evaluated. Gene expression of GALNT6, GALNT14, Gal-3, GDF-15, OCT4, SOX2, ABCC5, and β-catenin in tumor and adjacent non-tumor tissues (n = 30) was determined. The same was compared with GEO-microarray datasets. A significant increase in the expression of candidate genes was observed in BC tumor compared to adjacent non-tumor tissue; and in pre-therapeutic patients compared to post-therapeutic. GALNT6, GALNT14, Gal-3, and GDF-15 showed positive association with β-catenin, SOX2, OCT4, and ABCC5 and were significantly associated with poor Overall Survival. Our findings were also validated via in silico analysis. Our study suggests that GALNT6, GALNT14, and Gal-3 in association with GDF-15 promote stemness and intrinsic drug resistance in BC, possibly by β-catenin signaling pathway.

Keywords: Breast cancer; GALNT; drug resistance; galectin; stemness; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Growth Differentiation Factor 15* / genetics
  • Growth Differentiation Factor 15* / metabolism
  • Humans
  • Middle Aged
  • N-Acetylgalactosaminyltransferases* / genetics
  • N-Acetylgalactosaminyltransferases* / metabolism
  • Neoplastic Stem Cells / metabolism
  • Polypeptide N-acetylgalactosaminyltransferase*
  • beta Catenin* / genetics
  • beta Catenin* / metabolism

Substances

  • N-Acetylgalactosaminyltransferases
  • beta Catenin
  • Polypeptide N-acetylgalactosaminyltransferase
  • Growth Differentiation Factor 15
  • UDP-N-acetyl-D-galactosamine polypeptide N-acetylgalactosaminyltransferase 14, human
  • GDF15 protein, human
  • CTNNB1 protein, human