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- W2023788192 abstract "Proliferation and invasion of malignant tumor cells are mediated by multiple events, including activation of focal adhesion signalings and cytoskeleton remodeling. Focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2) are cytoplasmic tyrosine kinases identified as key mediators in regulation of cytoskeleton proteins in focal adhesion. Pyk2 were found to be overexpressed in Glioblastoma and played a central role in brain tumor invasion. Studies also showed that FAK increased expression and activation in various human cancers. Recently, studies with patients’ tumor samples have demonstrated that Pyk2 and FAK are co-overexpressed in over 70% human breast cancers from the very early disease stage of in situ carcinoma to the advanced metastatic stage. Pyk2 was also involved in the cytoskeleton changes initiated by heregulin through the ErbB-2 receptor in breast cancer cell lines. To further investigate role of Pyk2 and FAK in breast cancer progression and metastasis, we studied protein expression and activation of Pyk2 and FAK, as well as their substrates and interacting proteins in human breast cancer and normal breast epithelial cell lines. Our results showed that activation of both Pyk2 and FAK are marked increased in breast cancer cell lines in comparison with normal breast epithelial cells. In addition, serum stimulation was able to further activate Pyk2 and FAK and to increase tyrosine phosphorylation of their substrates and interacting proteins, including paxillin, Src, and p130CAS. The activated Pyk2 and FAK formed protein complex with paxillin, Src, and p130CAS. Our results and other published studies support the cooperative function of Pyk2 and FAK in breast cancer progression and suggest that dual inhibition of Pyk2 and FAK is a potential therapeutic approach for invasive breast cancer. Lead compounds of Pyk2 and FAK inhibitors have been identified by Southern Research drug discovery team and will be further evaluated in vitro and in vivo as potential breast cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1562." @default.
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- W2023788192 date "2010-04-15" @default.
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- W2023788192 title "Abstract 1562: PYK2 and FAK in breast cancer" @default.
- W2023788192 doi "https://doi.org/10.1158/1538-7445.am10-1562" @default.
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