Abstract 228: PAK1 kinase promotes cell motility through CRK serine phosphorylation in non-small cell lung cancer cells

Abstract

Abstract The role of c-Crk (CRK) in promoting metastasis is well described but the role of CRK phosphorylation and the corresponding signaling events are not well explained. We have noticed that CRK serine 41 phosphorylation is inversely correlated with p120-catenin and E-cadherin expressions in non-small cell lung cancer (NSCLC) cells. Therefore, we investigated the role of CRK serine 41 phosphorylation in the down-regulation of p120-catenin and cell motility in NSCLC cells. We prepared A549 cell lines stably expressing phosphomimetic and phosphodeficient CRK serine 41 constructs. A549 cells expressing phosphomimetic CRK seine 41 demonstrated a more aggressive behavior in would healing assay and on the contrary, expression of phosphodeficient CRK serine 41 in A549 cells reduced cell motility. A549 cells expressing phosphomimetic CRK serine 41 had lower p120-catenin mRNA and promoter activity and vice versa. In addition, we provide evidence that PAK1 mediates CRK serine 41 phosphorylation. RNAi mediated silencing of PAK1 increased p120-catenin level and also decreased cell motility in A549 and H157 cells. These effects were abrogated in A549 cells expressing phosphomimetic CRK serine 41. In summary, our data provide evidence for the role of PAK1 in promotion of cell motility and down regulation of p120-catenin through CRK serine 41 phosphorylation in NSCLC cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 228. doi:1538-7445.AM2012-228