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Anchorage‐independent phosphorylation of p130 Cas protects lung adenocarcinoma cells from anoikis
Author(s) -
Wei Lin,
Yang Yu,
Zhang Xin,
Yu Qiang
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10322
Subject(s) - anoikis , tyrosine phosphorylation , phosphorylation , proto oncogene tyrosine protein kinase src , cancer research , microbiology and biotechnology , tyrosine kinase , chemistry , biology , signal transduction , apoptosis , programmed cell death , biochemistry
The regulation and function of the signaling adaptor protein p130 Cas in tumor cell anchorage‐independent survival, or anoikis resistance, were investigated in human lung adenocarcinoma cells. The tyrosine phosphorylation and function of p130 Cas during cell detachment were analyzed in tumor cells and compared with that of normal epithelial cells. Cell detachment trigged rapid dephosphorylation of p130 Cas in the nontumorigenic and anoikis‐sensitive normal epithelial cells, but had no effect on the tyrosine phosphorylation of p130 Cas in the anoikis‐resistant lung adenocarcinoma cells. Further analysis revealed that the total tyrosine kinase activities associated with p130 Cas in the lung tumor cells are anchorage‐independent and are significantly higher than that in the normal cells, in which the p130 Cas ‐associated tyrosine kinase activities are anchorage‐dependent. Analysis of two known p130 Cas ‐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 p130 Cas and induced anoikis. Furthermore, overexpression of dominant‐negative forms of p130 Cas also induced apoptosis. Taken together, these data suggest that p130 Cas mediates a cell survival signal from cell–matrix interaction. Alterations in tumor cells that lead to constitutive phosphorylation of p130 Cas 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.