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Myosin-interacting guanine exchange factor (MyoGEF) regulates the invasion activity of MDA-MB-231 breast cancer cells through activation of RhoA and RhoC

Oncogene volume 28, pages 2219–2230 (2009)Cite this article

Abstract

The small guanine triphosphatase (GTPase) proteins RhoA and RhoC are essential for tumor invasion and/or metastasis in breast carcinomas. However, it is poorly understood how RhoA and RhoC are activated in breast cancer cells. Here we describe the role of myosin-interacting guanine nucleotide exchange factor (MyoGEF) in regulating RhoA and RhoC activation as well as cell polarity and invasion in an invasive breast cancer cell line MDA-MB-231. RNA-interference (RNAi)-mediated depletion of MyoGEF in MDA-MB-231 cells not only suppresses the activation of RhoA and RhoC, but also decreases cell polarity and invasion activity. The dominant-negative mutants of RhoA and RhoC, but not Rac1 and Cdc42, dramatically decrease actin polymerization induced by MyoGEF. In addition, MyoGEF colocalizes with nonmuscle myosin IIA (NMIIA) to the front of migrating cells, and depletion of NMIIA by RNAi disrupts the polarized localization of MyoGEF at the cell leading edge, suggesting a role for NMIIA in regulating MyoGEF localization and function. Moreover, MyoGEF protein levels significantly increase in infiltrating ductal carcinomas as well as in invasive breast cancer cell lines. Taken together, our results suggest that MyoGEF cooperates with NMIIA to regulate the polarity and invasion activity of breast cancer cells through activation of RhoA and RhoC.

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Acknowledgements

We thank Dr Robert S Adelstein and Dr Mary Anne Conti for their critical reading and comments on the manuscript. We thank Dr Keith Burridge (University of North Carolina at Chapel Hill, Chapel Hill, NC, USA) and Dr Rick Cerione (Cornell University, Ithaca, NY, USA) for providing GST-RBD and GST-PBD plasmids. This publication was made possible by National Institutes of Health (NIH) Grant no. P20 RR015563 from the National Center for Research Resources. This work was also supported by NIHGrant k22 HL071542 (to QW), as well as a fund from Terry C. Johnson Center for Basic Cancer Research (to QW). This is contribution 09-136-J from the Kansas Agricultural Experiment Station, Manhattan, KS, USA.

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    D Wu, M Asiedu & Q Wei

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Correspondence to Q Wei.

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Wu, D., Asiedu, M. & Wei, Q. Myosin-interacting guanine exchange factor (MyoGEF) regulates the invasion activity of MDA-MB-231 breast cancer cells through activation of RhoA and RhoC. Oncogene 28, 2219–2230 (2009). https://doi.org/10.1038/onc.2009.96

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