BAG-1 accelerates cell motility of human gastric cancer cells

Oncogene. 1999 May 27;18(21):3244-51. doi: 10.1038/sj.onc.1202661.

Abstract

BAG-1 is a Hsp70/Hsc70-binding protein that interacts with Bcl-2, Raf-1, steroid hormone receptors, Siah-1, and hepatocyte growth factor (HGF) receptors, implying multiple functions for the BAG-1 protein. Here, we provide evidence that gene transfer-mediated overexpression of BAG-1 markedly enhances the motility of human gastric cancer cells. Two independent in vitro migration assays showed that the BAG-1-expressing MKN74 cells exhibited more active migration compared with control transfectants or parent MKN74 cells. In MKN74 cells, the overexpression of BAG-1 affected neither cell adhesion capability nor migration responses to HGF. The promotive effect of BAG-1 on cell migration was similarly observed in transfectants of another human gastric cancer MKN45 cell line. In BAG-1 transfected gastric cancer MKN74 cells, BAG-1 colocalized with cytokeratin as well as actin filaments, and was concentrated at membrane ruffles induced by lysophosphatidic acid (LPA). Taken together, these studies demonstrate that BAG-1 has a novel function as promoter of cell migration in human gastric cancer cells, possibly through cooperation with cytoskeletal proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Cell Adhesion / physiology
  • Cell Movement / physiology*
  • Culture Media
  • DNA-Binding Proteins
  • Humans
  • Keratins / metabolism
  • Mice
  • Serum Albumin, Bovine
  • Stomach Neoplasms / physiopathology*
  • Transcription Factors
  • Tumor Cells, Cultured

Substances

  • Actins
  • BCL2-associated athanogene 1 protein
  • Carrier Proteins
  • Culture Media
  • DNA-Binding Proteins
  • Transcription Factors
  • Serum Albumin, Bovine
  • Keratins