Abstract 2356: The role of the Rac GTPases in PC-3 prostate cancer cell diapadesis

Autor: Linda Sequeira, Moumita Chatterjee, Surabhi Pathak, Cara W. Dubyk, Kenneth L. van Golen
Rok vydání: 2010
Předmět:
Zdroj: Cancer Research. 70:2356-2356
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.am10-2356
Popis: The Rho GTPases are molecular switches intimately involved in cancer metastasis through orchestrating changes in the cytoskeleton leading to motility and invasion. Previously, we demonstrated that RhoC GTPase was sufficient and required for PC-3 prostate cancer invasion. Furthermore, we demonstrated that targeted down-regulation of RhoC using either a dominant-negative RhoC or by specific shRNAs led to increased and sustained activation of Rac1 GTPase. Increased levels of active Rac1 led to morphological, molecular and phenotypic changes reminiscent of epithelial to mesenchymal transition (EMT). Additionally, we demonstrated a requirement for active Rac1 GTPase in PC-3 tumor cell diapedesis across a bone marrow endothelial cell (BMEC) layer, an important step in prostate cancer skeletal metastasis. In the current study, we analyze the specific roles of Rac1, Rac3 and RhoG GTPases in tumor cell diapadesis. Use of specific siRNAs to down-regulate the individual Rac proteins demonstrated unique roles for each in promoting cell adhesion and diapedesis. We found Rac1 to be expressed at significantly higher levels than Rac3 or RhoG. However, RhoG appears to regulate PC-3 diapadesis at levels similar to Rac1. In contrast, Rac3 does not regulate diapadesis but controls PC-3 binding to substrates and BMECs. Together, these data suggest a role for coordinated activity of the Rac GTPases during diapadesis. 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 2356.
Databáze: OpenAIRE
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