Reference - Detail
RRC ID | 43171 |
---|---|
Author | Li H, Cai X, Fan X, Moquin B, Stoicov C, Houghton J. |
Title | Fas Ag-FasL coupling leads to ERK1/2-mediated proliferation of gastric mucosal cells. |
Journal | Am J Physiol Gastrointest Liver Physiol |
Abstract |
When cells within the gastric mucosa progress from metaplasia to dysplasia to cancer, they acquire a Fas Ag apoptosis-resistant phenotype. It is unusual to completely abolish the pathway, suggesting other forms of Fas Ag signaling may be important or even necessary for gastric cancer to progress. Little is known about alternate signaling of the Fas Ag pathway in gastric mucosal cells. Using a cell culture model of rat gastric mucosal cells, we show that gastric mucosal cells utilize a type II signaling pathway for apoptosis. Under conditions of low receptor stimulation or under conditions where apoptosis is blocked downstream of the death-inducing signal complex, Fas Ag signaling proceeds toward proliferative signaling. Under conditions favoring proliferative signaling, cFLIP is recruited to the Fas-associated death domain-like interleukin-1beta-converting enzyme at the death-inducing signal complex and activates ERK1/2. ERK1/2 in turn activates NF-kappaB. ERK1/2 stimulates proliferation, whereas NF-kappaB activation results in upregulation of the antiapoptotic protein survivin, further promoting proliferation over apoptosis. These results suggest that factors that inhibit apoptosis confer a growth advantage to the cells beyond the survival advantage of avoiding apoptosis and in effect convert the Fas Ag signaling pathway from a tumor suppressor to a tumor promoter. |
Volume | 294(1) |
Pages | G263-75 |
Published | 2008-1-1 |
DOI | 10.1152/ajpgi.00267.2007 |
PII | 00267.2007 |
PMID | 17991709 |
MeSH | Animals Apoptosis CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism Cell Line, Tumor Cell Proliferation* Cell Transformation, Neoplastic / immunology Cell Transformation, Neoplastic / metabolism* Cell Transformation, Neoplastic / pathology Death Domain Receptor Signaling Adaptor Proteins / metabolism Epithelial Cells / enzymology Epithelial Cells / immunology Epithelial Cells / metabolism* Epithelial Cells / pathology Fas Ligand Protein / metabolism* Gastric Mucosa / enzymology Gastric Mucosa / immunology Gastric Mucosa / metabolism* Gastric Mucosa / pathology Humans MAP Kinase Kinase Kinases / metabolism Mice Mitogen-Activated Protein Kinase 1 / metabolism* Mitogen-Activated Protein Kinase 3 / metabolism* NF-kappa B / metabolism Phosphorylation Rats Recombinant Fusion Proteins / metabolism Signal Transduction Time Factors Transfection fas Receptor / genetics fas Receptor / metabolism* |
IF | 3.725 |
Times Cited | 21 |
WOS Category | GASTROENTEROLOGY & HEPATOLOGY PHYSIOLOGY |
Resource | |
Human and Animal Cells | RGM1(RCB0876) |