Characterization of the roles of RHOC and RHOA GTPases in invasion, motility, and matrix adhesion in inflammatory and aggressive breast cancers.
BACKGROUND
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.


METHODS
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.


RESULTS
RHOC, and not RHOA, modulates surface expression and colocalization of alpha2 and beta1 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.


CONCLUSIONS
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.
Wu
Mei
M
Department of Internal Medicine, Division of Hematology and Oncology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan.
Wu
Zhi-Fen
ZF
Rosenthal
Devin T
DT
Rhee
Elliot M
EM
Merajver
Sofia D
SD
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D002465:Cell Movement; D002999:Clone Cells; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000494:pharmacology; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology*; D000075024:rhoC GTP-Binding Protein
D034741:RNA, Small Interfering; C066737:RHOA protein, human; D020559:Monomeric GTP-Binding Proteins; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein