Myosin-interacting guanine exchange factor (MyoGEF) regulates the invasion activity of MDA-MB-231 breast cancer cells through activation of RhoA and RhoC
Open Access
- 4 May 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 28 (22), 2219-2230
- https://doi.org/10.1038/onc.2009.96
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.Keywords
This publication has 66 references indexed in Scilit:
- Centrosome/Spindle Pole–associated Protein Regulates Cytokinesis via Promoting the Recruitment of MyoGEF to the Central SpindleMolecular Biology of the Cell, 2009
- Phosphorylation of MyoGEF on Thr-574 by Plk1 Promotes MyoGEF Localization to the Central SpindlePublished by Elsevier BV ,2008
- Regulation of protrusion, adhesion dynamics, and polarity by myosins IIA and IIB in migrating cellsThe Journal of cell biology, 2007
- Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA leading to localized inhibition of contractilityThe Journal of cell biology, 2006
- The Role of Myosin II Motor Activity in Distributing Myosin Asymmetrically and Coupling Protrusive Activity to Cell TranslocationMolecular Biology of the Cell, 2006
- The Rho-mDia1 Pathway Regulates Cell Polarity and Focal Adhesion Turnover in Migrating Cells through Mobilizing Apc and c-SrcMolecular and Cellular Biology, 2006
- Nonmuscle Myosin IIB Is Involved in the Guidance of Fibroblast MigrationMolecular Biology of the Cell, 2004
- The Mouse Formin mDia1 Is a Potent Actin Nucleation Factor Regulated by AutoinhibitionCurrent Biology, 2003
- Formins Set the Record StraightScience, 2002
- Rac1-Induced Endocytosis Is Associated with Intracellular Proteolysis during Migration through a Three-Dimensional MatrixExperimental Cell Research, 2000