GXYLT2 accelerates cell growth and migration by regulating the Notch pathway in human cancer cells

Exp Cell Res. 2019 Mar 1;376(1):1-10. doi: 10.1016/j.yexcr.2019.01.023. Epub 2019 Feb 1.

Abstract

Glucoside xylosyltransferase2 (GXYLT2), a member of the human α-1,3-D-xylosyltransferases, functions to modify the first xylose to the O-Glucose residue on epidermal growth factor (EGF) repeats of Notch receptors. It is well-established that the Notch signaling pathway plays a critical role in proper development and homeostasis. However, the regulatory role of EGF xylosylation in Notch signaling and different cell activities in human cells remains unknown. In this study, we showed that knockdown of GXYLT2 suppressed human cell proliferation and induced G1/S phase cell cycle arrest. GXYLT2 downregulation also inhibited cell migration and invasion, whereas the overexpression of GXYLT2 had the opposite effects. Additionally, GXYLT2 activated Notch signaling and promoted the phosphorylation of MAPKs but not PI3K and Akt. Taken together, our findings indicated that GXYLT2 plays an important role in cell activities via regulation of the Notch signaling.

Keywords: GXYLT2; MAPK; Migration; Notch signaling; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Epidermal Growth Factor / genetics
  • Female
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Glucose / genetics
  • Glycosyltransferases / genetics*
  • Humans
  • Pentosyltransferases / genetics
  • Pentosyltransferases / physiology*
  • Receptors, Notch / genetics
  • Xylose / genetics

Substances

  • Receptors, Notch
  • Epidermal Growth Factor
  • Xylose
  • Glycosyltransferases
  • Pentosyltransferases
  • GXYLT2 protein, human
  • Glucose