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Characterization of the roles of RHOC and RHOA GTPases in invasion, motility, and matrix adhesion in inflammatory and aggressive breast cancers
Article first published online: 19 MAY 2010
Copyright © 2010 American Cancer Society
Supplement: Proceedings of the First International Inflammatory Breast Cancer Conference, Supplement to Cancer
Volume 116, Issue Supplement 11, pages 2768–2782, 1 June 2010
How to Cite
Wu, M., Wu, Z.-f., Rosenthal, D. T., Rhee, E. M. and Merajver, S. D. (2010), Characterization of the roles of RHOC and RHOA GTPases in invasion, motility, and matrix adhesion in inflammatory and aggressive breast cancers. Cancer, 116: 2768–2782. doi: 10.1002/cncr.25181
- Issue published online: 19 MAY 2010
- Article first published online: 19 MAY 2010
- Manuscript Accepted: 16 FEB 2010
- Manuscript Revised: 2 FEB 2010
- Manuscript Received: 6 JAN 2010
The 2 closely related small GTPases, RHOC and RHOA, are involved in mammary gland carcinogenesis; however, their specific roles in determining cancer cell adhesion and invasion have not been elucidated.
RHOA and RHOC are highly homologous, thereby posing a major challenge to study their individual functions in cancer cells. By selectively knocking down these proteins, we have been able to alternatively inhibit RHOC and RHOA, while preserving expression of the other rho protein. Quantitative analyses of the growth patterns and invasion in the aggressive estrogen receptor negative cell lines MDA-231 and SUM149 were carried out on collagen I and Matrigel substrates.
RHOC, and not RHOA, modulates surface expression and colocalization of α2 and β1 integrins in MDA-MB-231 on collagen I. Neither RHOC or RHOA affected integrin expression in the inflammatory breast cancer cell line SUM149, further highlighting the different regulation of adhesion and motility in inflammatory breast cancer.
This work shows that RHOC and RHOA play different roles in cell-matrix adhesion, motility, and invasion of MDA-MB-231 and reaffirms the crucial role of RHOC-GTPase in inflammatory breast cancer cell invasion. Cancer 2010;116(11 suppl):2768–82. © 2010 American Cancer Society.