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Detachment-mediated resistance to TRAIL-induced apoptosis is associated with stimulation of the PI3K/Akt pathway in fetal and adenocarcinoma epithelial colon cells
L. Kočí, M. Hýžd'alová, A. Vaculová, J. Hofmanová, A. Kozubík,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
NT11201
MZ0
CEP Register
- MeSH
- Adenocarcinoma enzymology pathology MeSH
- Enzyme Activation drug effects MeSH
- Anoikis drug effects MeSH
- Cell Adhesion drug effects MeSH
- Cell Membrane drug effects metabolism MeSH
- HT29 Cells MeSH
- Drug Resistance, Neoplasm drug effects MeSH
- Epithelial Cells drug effects enzymology pathology MeSH
- Focal Adhesion Protein-Tyrosine Kinases metabolism MeSH
- Phosphatidylinositol 3-Kinases metabolism MeSH
- Phosphorylation drug effects MeSH
- Humans MeSH
- Colonic Neoplasms enzymology pathology MeSH
- Fetus cytology MeSH
- TNF-Related Apoptosis-Inducing Ligand pharmacology MeSH
- Protein Serine-Threonine Kinases metabolism MeSH
- Proto-Oncogene Proteins c-akt metabolism MeSH
- Receptors, Death Domain metabolism MeSH
- Signal Transduction drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The resistance of transformed epithelial cells to a detachment-induced apoptosis (anoikis) can significantly affect their susceptibility to anticancer therapy. We showed that detachment of both fetal (FHC) and adenocarcinoma (HT-29) human colon epithelial cells resulted in the activation of the pro-survival Akt pathway, and significant changes in integrin-linked kinase (ILK) and focal adhesive kinase (FAK) phosphorylation. We demonstrated a detachment-induced and PI3K/Akt-mediated resistance to apoptotic effects of TRAIL, which was not associated with any changes in the cell surface TRAIL death receptor levels. Instead, a modulation of downstream intracellular signaling events was suggested to be involved. Our results may have important implications for optimization of new strategies in treatment of cancers at different stages of development.
References provided by Crossref.org
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