A role of fukutin, a gene responsible for Fukuyama type congenital muscular dystrophy, in cancer cells: a possible role to suppress cell proliferation

Int J Exp Pathol. 2008 Oct;89(5):332-41. doi: 10.1111/j.1365-2613.2008.00599.x.

Abstract

Fukutin, a gene responsible for Fukuyama type congenital muscular dystrophy (FCMD), is presumably related to the glycosylation of alpha-dystroglycan (alpha-DG), involved in basement membrane formation. Hypoglycosylation of alpha-DG plays a key role for the pathogenesis of FCMD. On the other hand, fukutin and alpha-DG are also expressed in various non-neuromuscular tissues. Recently, a role of alpha-DG as a cancer suppressor has been proposed, because of a decrease of glycosylated alpha-DG in cancers. In this study, function of fukutin was investigated in two cancer cell lines, focusing on whether fukutin is involved in the glycosylation of alpha-DG in cancer cells and has any possible roles related to a cancer suppressor. Localization of fukutin and a result of laminin-binding assay after RNA interference suggest that fukutin may be involved in the glycosylation of alpha-DG in a small portion in these cancer cell lines. In Western blotting and immuno-electron microscopy, localization of fukutin in the nucleus was suggested in addition to the Golgi apparatus and/or endoplasmic reticulum. Immunohistochemically, there were more Ki-67-positive cells and more nuclear staining of phosphorylated c-jun after knockdown of fukutin in two cell lines. Fukutin appears to suppress cell proliferation through a system involving c-jun, although it is unclear this process is related to alpha-DG or not at present. The result may propose a possibility of another function of fukutin in addition to the glycosylation of alpha-DG in cancer cells.

MeSH terms

  • Blotting, Western / methods
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Dystroglycans / metabolism
  • Glycosylation
  • HeLa Cells
  • Humans
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Microscopy, Immunoelectron
  • Muscular Dystrophies / metabolism
  • RNA Interference
  • RNA, Small Interfering / pharmacology

Substances

  • FKTN protein, human
  • Membrane Proteins
  • RNA, Small Interfering
  • Dystroglycans