Anchorage‐independent phosphorylation of p130Cas protects lung adenocarcinoma cells from anoikis

• DOI: 10.1002/jcb.10322
• Publication Date: 2002-11-22T15:29:21Z
• Authors: Lin Wei; Yu Yang; Xin Zhang; Qiang Yu
• Keywords: 0301 basic medicine; Lung Neoplasms; Dose-Response Relationship, Drug; Cell Survival; Immunoblotting; Apoptosis; Bronchi; Adenocarcinoma; Anoikis; Phosphoproteins; Precipitin Tests; Cell Line; 03 medical and health sciences; Crk-Associated Substrate Protein; Dogs; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Animals; Humans; Neoplasm Metastasis; Phosphorylation; Plasmids

AbstractThe regulation and function of the signaling adaptor protein p130Cas in tumor cell anchorage‐independent survival, or anoikis resistance, were investigated in human lung adenocarcinoma cells. The tyrosine phosphorylation and function of p130Cas during cell detachment were analyzed in tumor cells and compared with that of normal epithelial cells. Cell detachment trigged rapid dephosphorylation of p130Cas in the nontumorigenic and anoikis‐sensitive normal epithelial cells, but had no effect on the tyrosine phosphorylation of p130Cas in the anoikis‐resistant lung adenocarcinoma cells. Further analysis revealed that the total tyrosine kinase activities associated with p130Cas in the lung tumor cells are anchorage‐independent and are significantly higher than that in the normal cells, in which the p130Cas‐associated tyrosine kinase activities are anchorage‐dependent. Analysis of two known p130Cas‐associated tyrosine kinases FAK and Src indicated that the regulation of tyrosine phosphorylation of FAK and Src are altered in the tumor cells. Inhibition of Src specifically abolished phosphorylation of p130Cas and induced anoikis. Furthermore, overexpression of dominant‐negative forms of p130Cas also induced apoptosis. Taken together, these data suggest that p130Cas mediates a cell survival signal from cell–matrix interaction. Alterations in tumor cells that lead to constitutive phosphorylation of p130Cas can prevent cells from anoikis, hence contribute to tumor cell anchorage independence and metastasis. J. Cell. Biochem. 87: 439–449, 2002. © 2002 Wiley‐Liss, Inc.