BAG-1 accelerates cell motility of human gastric cancer cells.
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.
Naishiro
Y
Y
First Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Adachi
M
M
Okuda
H
H
Yawata
A
A
Mitaka
T
T
Takayama
S
S
Reed
J C
JC
Hinoda
Y
Y
Imai
K
K
D000199:Actins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D003470:Culture Media; D004268:DNA-Binding Proteins; D006801:Humans; D007633:Keratins / Q000378:metabolism; D051379:Mice; D012710:Serum Albumin, Bovine; D013274:Stomach Neoplasms / Q000503:physiopathology*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D000199:Actins; C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D003470:Culture Media; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D012710:Serum Albumin, Bovine; D007633:Keratins