Enhanced intrinsic migration of aggressive breast cancer cells by inhibition of Rac1 GTPase.
Rac GTPases are known to play a crucial role in regulating cytoskeletal changes necessary for cell migration. Migration has been shown to be positively regulated by Rac in most cell types. However, there is also a large body of conflicting evidence in some other cell types with respect to the role of Rac in migration, suggesting that Rac GTPases regulate cell migration in a cell type-dependent manner. In the present study, we have characterized the effects of Rac1 GTPase inhibition on the migratory abilities of a number of breast cancer cell lines with differential degrees of tumorigenic and metastatic potentials. We show that Rac1 inhibition in non-metastatic (MCF-7, T-47D) or moderately metastatic (Hs578T) cell lines results in inhibition of migration, whereas in highly metastatic cell lines (MDA-MB-435, MDA-MB-231, and C3L5) Rac1 inhibition results in stimulation of migration. This stimulation of migration following Rac1 inhibition is also accompanied by the enhanced RhoA activity, suggesting a possible existence of a dominating role of RhoA over Rac1 in regulating intrinsic migration of the highly metastatic breast cancer cells.
Zuo
Yufeng
Y
Department of Pathology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building H422, London, ON, Canada N6A 5C1.
Shields
Sarah-Kim
SK
Chakraborty
Chandan
C
D000634:Aminoquinolines / Q000494:pharmacology*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011743:Pyrimidines / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D000634:Aminoquinolines; C487513:NSC 23766; D011743:Pyrimidines; D034741:RNA, Small Interfering; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein