RGD Reference Report - Transforming growth factor-alpha prevents detachment-induced inhibition of c-Src kinase activity, Bcl-XL down-regulation, and apoptosis of intestinal epithelial cells. - Rat Genome Database

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Transforming growth factor-alpha prevents detachment-induced inhibition of c-Src kinase activity, Bcl-XL down-regulation, and apoptosis of intestinal epithelial cells.

Authors: Rosen, K  Coll, ML  Li, A  Filmus, J 
Citation: Rosen K, etal., J Biol Chem 2001 Oct 5;276(40):37273-9.
RGD ID: 730227
Pubmed: PMID:11487584   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M106424200   (Journal Full-text)

Detachment of epithelial cells from the extracellular matrix (ECM) results in apoptosis, a phenomenon often referred to as anoikis. Acquisition of anoikis resistance is now thought to be a prerequisite for the progression of carcinomas. Colorectal cancer cells frequently secrete epidermal growth factor receptor (EGFR) ligands, which are known to have anti-apoptotic activity. However, whether these ligands have the ability to inhibit anoikis of intestinal epithelial cells is unclear, since at least in some cell types efficient EGFR signaling requires cell-ECM adhesion. Here we report that transforming growth factor-alpha (TGF-alpha), an EGFR ligand that is frequently secreted by colorectal cancer cells, strongly inhibits anoikis of the non-malignant rat intestinal epithelial cell lines, IEC-18 and RIE-1. TGF-alpha exerts its anti-anoikis effect by preventing detachment-induced inhibition of c-Src kinase activity. We also show that Fas activation, a molecular event known to play a critical role in anoikis, is not suppressed by TGF-alpha. On the other hand, this growth factor strongly inhibits the detachment-induced down-regulation of Bcl-X(L), another change that is involved in the induction of anoikis. We further demonstrate that this inhibition occurs in a c-Src-dependent manner. We conclude that TGF-alpha has the ability to suppress anoikis of intestinal epithelial cells, at least in part, by reverting the loss of c-Src activity and Bcl-X(L) expression induced by detachment from the ECM.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of apoptotic process  IDA 730227 RGD 
negative regulation of cellular process  IDA 730227 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
extracellular space  IDA 730227 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
epidermal growth factor receptor binding  TAS 730227 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tgfa  (transforming growth factor alpha)


Additional Information