Fas Ag-FasL coupling leads to ERK1/2-mediated proliferation of gastric mucosal cells
UMass Chan Affiliations
Department of Medicine, Division of GastroenterologyDocument Type
Journal ArticlePublication Date
2007-11-10Keywords
AnimalsAntigens, CD95
Apoptosis
CASP8 and FADD-Like Apoptosis Regulating Protein
Cell Line, Tumor
*Cell Proliferation
Cell Transformation, Neoplastic
Death Domain Receptor Signaling Adaptor Proteins
Epithelial Cells
Fas Ligand Protein
Gastric Mucosa
Humans
MAP Kinase Kinase Kinases
Mice
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
NF-kappa B
Phosphorylation
Rats
Recombinant Fusion Proteins
Signal Transduction
Time Factors
Transfection
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
2007 Nov 8. Link to article on publisher's siteDOI
10.1152/ajpgi.00267.2007Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39155PubMed ID
17991709Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1152/ajpgi.00267.2007
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