Functional role of glycosphingolipids in contact inhibition of growth in a human mammary epithelial cell line

FEBS Lett. 2017 Jul;591(13):1918-1928. doi: 10.1002/1873-3468.12709. Epub 2017 Jun 22.

Abstract

We have demonstrated previously the involvement of certain glycosphingolipids (GSLs) in 'contact inhibition' (dependent on cell-to-cell contact) of cell growth. Here, we examined the roles of specific GSLs in contact inhibition of the human epithelial cell line MCF10A. Contact-inhibited cells show increased expression of the ganglioside GD3 and the globo-series GSL Gb3, and of the mRNAs for the corresponding sialyltransferases ST8SIA1 (GD3 synthase) and galactosyltransferase A4GALT (Gb3 synthase). siRNA knockdown (KD) of ST8SIA1 and/or A4GALT significantly suppresses contact inhibition. Exogenous addition of GD3 or Gb3 inhibits proliferation of low-density cells. Our findings suggest that GSLs play functional roles in contact inhibition of these cells and that Merlin/NF2, a tumor suppressor protein, is involved in the GSL function.

Keywords: Merlin/NF2; contact inhibition of cell growth; glycosphingolipids; human mammary epithelial cells.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Count
  • Cell Line, Tumor
  • Cell Proliferation
  • Contact Inhibition*
  • Galactosyltransferases / deficiency
  • Galactosyltransferases / genetics
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Glycosphingolipids / metabolism*
  • Humans
  • Mammary Glands, Human / cytology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Sialyltransferases / deficiency
  • Sialyltransferases / genetics

Substances

  • Glycosphingolipids
  • RNA, Messenger
  • RNA, Small Interfering
  • Galactosyltransferases
  • UDP-galactose-lactosylceramide alpha 1-4-galactosyltransferase
  • Sialyltransferases
  • alpha-N-acetylneuraminate alpha-2,8-sialyltransferase