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- W2016177423 abstract "Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCVimentin is a dynamic type III intermediate filament that is overexpressed in various cancers including non-small cell lung cancer (NSCLC). It is a classic biomarker for highly invasive tumors and is associated with increased likelihood of metastasis and poor survival. Vimentin filaments are dynamic and localize to focal adhesions, where they assemble and disassemble to promote cell migration. Our data show that vimentin depletion reduces cell adhesion and phosphorylated focal adhesion kinase (pFAK); therefore, we hypothesize that vimentin acts through FAK to regulate cell adhesion and metastasis. We show that vimentin filaments enter pFAK- and pSrc-positive focal adhesion sites, and upon vimentin depletion, pFAK, pSrc and total FAK levels decrease. To explore the mechanism behind this observation, we performed a phospho-proteomic screen for proteins whose phosphorylation is altered upon vimentin loss. One of the identified proteins was a guanine nucleotide exchange factor (GEF) that regulates rac1. We show that vimentin loss leads to GEF mis-localization and downstream rac1 inactivation. Furthermore, inactivation of the GEF itself resulted in aberrant cellular adhesion and loss of pFAK. Based upon this data, we propose that vimentin serves as a signaling scaffold to regulate FAK via a rac1-GEF interaction. This work provides insight into the mechanism by which vimentin affects cell adhesion and potentially NSCLC metastasis.Citation Format: Lauren Havel, Adam I. Marcus. Vimentin serves as a signaling scaffold at focal adhesion sites to regulate lung cancer cell adhesion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 282. doi:10.1158/1538-7445.AM2013-282" @default.
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- W2016177423 date "2013-02-01" @default.
- W2016177423 modified "2023-09-26" @default.
- W2016177423 title "Abstract A52: Vimentin serves as a signaling scaffold at focal adhesion sites to regulate lung cancer cell adhesion" @default.
- W2016177423 doi "https://doi.org/10.1158/1538-7445.tim2013-a52" @default.
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