title: Detachment-mediated resistance to TRAIL-induced apoptosis is associated with stimulation of the PI3K/Akt pathway in fetal and adenocarcinoma epithelial colon cells.
abstract: 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.
authors.affiliation: Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i., Brno, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Kočí
authors.forename: Martina
authors.initials: M
authors.lastname: Hýžd'alová
authors.forename: Alena
authors.initials: A
authors.lastname: Vaculová
authors.forename: Jiřina
authors.initials: J
authors.lastname: Hofmanová
authors.forename: Alois
authors.initials: A
authors.lastname: Kozubík
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology; D023102:Anoikis / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D005333:Fetus / Q000166:cytology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D053218:Receptors, Death Domain / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D000099200:Scaffold Protein ILK
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D053218:Receptors, Death Domain; D053221:TNF-Related Apoptosis-Inducing Ligand; D000099200:Scaffold Protein ILK