Abstract 1451: Inhibition of cell migration via reduced phosphorylation of focal adhesion kinase by TIS21/BTG2/PC3 in A549 cells

Abstract

Abstract It has been reported that TPA inducible sequence 21 (TIS21/BTG2/PC3) functions as a tumor suppressor in carcinogenesis of thymus, prostate, kidney, and liver. Although the expression of TIS21 is down-regulated in primary and metastatic cancers, the role of TIS21/BTG2/PC3 in cell migration and metastasis remains to be elucidated. In this study, we report a role of TIS21 in cancer cell migration. We observed that TIS21 inhibited cell migration and invasion in A549 lung cancer cells. Consistent with this observation, phosphorylation of focal adhesion kinase (FAK) on Y576 and Y925 residues, but not Y397, was markedly inhibited by over-expression of TIS21, which residues are known to be phosphorylated by activated Src. It has been known that activity of Src can be regulated either by phosphorylation at Y416 or oxidation of the molecule. Phosphorylation of Src on Y416 was not regulated by overexpression of TIS21 in A549 cells, whereas TIS21 significantly inhibited Src activity by reducing the generation of reactive oxygen species. In addition to that TIS21 down-regulated matrix metalloproteinase-2 (MMP-2) expression in A549 cells. In summary, therefore, we can suggest that TIS21 down-regulates FAK activity via inhibiting Src activation and reduces expression of MMP-2, resulting in antimetastatic phenomenon in cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1451. doi:10.1158/1538-7445.AM2011-1451