Abstract
Abstract Lung cancer is the leading cause of cancer death in the United States. Specifcally, non-small cell lung cancer (NSCLC) is responsible for about 80% of lung cancer deaths and has a 5-year survival rate of only 15-25%. This poor survival statistic results from diagnosis at advanced stages of the disease when metastasis of the primary tumor has already occurred; therefore, identifying the molecular mechanisms guiding metastasis is crucial for advances in treatment. The intermediate filament vimentin is overexpressed in metastatic cancers and its expression correlates with increased invasive capacity and reduced patient survival. A population of vimentin filaments localizes to focal adhesions, which attach to the extracellular matrix and are required for cell motility. Focal adhesions are composed of a complex of proteins, including focal adhesion kinase (FAK), which is overexpressed in NSCLC. Since evidence suggests that both FAK and vimentin co-localize at focal adhesions, we hypothesize that vimentin acts through FAK to regulate cell adhesion and thereby cell migration. Our results show that vimentin depletion leads to decreased cell adhesion and migration, with decreased FAK activation and expression. We show that vimentin filaments directly enter total FAK and pFAK- Y397 sites at the cellular leading edge of motile lung cancer cells. Using immunoprecipitation, we show vimentin interacts with several members of the focal adhesion complex, suggesting that vimentin can regulate focal adhesion activity. To address the mechanism by which this may occur, we hypothesize that the phosphorylation state of vimentin, which is important for cell migration, is crucial for proper functioning at focal adhesions. This is the focus of our future work with the goal of identifying potential new therapeutic targets to block metastasis and improve lung cancer patients’ prognosis. 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 5172. doi:1538-7445.AM2012-5172
Published Version
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