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Reduced focal adhesion kinase and paxillin phosphorylation in BCR‐ABL‐transfected cells
Author(s) -
Cheng Keding,
Kurzrock Razelle,
Qiu Xiangguo,
Estrov Zeev,
Ku Stella,
Dulski Kim M.,
Wang Jean Y. J.,
Talpaz Moshe
Publication year - 2002
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.10670
Subject(s) - paxillin , focal adhesion , transfection , ptk2 , microbiology and biotechnology , tyrosine phosphorylation , phosphorylation , fibronectin , abl , cancer research , tyrosine kinase , biology , extracellular matrix , cell culture , signal transduction , protein kinase a , mitogen activated protein kinase kinase , genetics
Abstract BACKGROUND BCR‐ABL formation is critical to oncogenic transformation in chronic myelogenous leukemia and has been implicated as a key event leading to alterations in cytoskeletal structures and adhesion in the leukemic cells. The authors therefore investigated the effect of p210 BCR‐ABL on actin polymerization as well as on the expression and phosphorylation state of the adhesion proteins paxillin and focal adhesion kinase (FAK). METHODS Transfection with BCR‐ABL constructs abrogated the ability of NIH 3T3 fibroblasts to adhere and the cells underwent striking morphologic changes. RESULTS Scanning electron microscopy revealed that the cells lost their elongated appearance and became rounded. This alteration was associated with significantly reduced actin polymerization. In addition, steady‐state levels of paxillin and FAK protein were increased. However, while the overall level of phosphotyrosines was also increased, the amount of tyrosine phosphorylated paxillin and FAK was reduced in the BCR‐ABL‐transfected cells as compared to the parental cells. Culture on extracellular fibronectin matrix partially reversed the morphologic changes and resulted in a return, albeit incomplete, of filamentous actin in BCR‐ABL‐transfected 3T3 fibroblasts. In addition, phosphorylation of paxillin and FAK in the BCR‐ABL‐transfected NIH 3T3 cells was restored. CONCLUSIONS The authors conclude that, in the current system, transfection of BCR‐ABL attenuates FAK and paxillin phosphorylation and reduces actin polymerization, events accompanied by significant alterations in cellular morphology. The observation that exposure of the cells to fibronectin partially reverses all these changes suggests that the focal adhesion proteins and actin structures nevertheless remain responsive to singnaling from the outside. Cancer 2002;95:440–50. © 2002 American Cancer Society. DOI 10.1002/cncr.10670