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 o...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2006-12, Vol.351 (2), p.361-367
Main Authors: Zuo, Yufeng, Shields, Sarah-Kim, Chakraborty, Chandan
Format: Article
Language:English
Subjects:
Aminoquinolines - pharmacology
Breast cancer
Breast Neoplasms
Cell Line, Tumor
Cell migration
Cell Movement - drug effects
Cell Movement - physiology
Female
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Pyrimidines - pharmacology
Rac1
rac1 GTP-Binding Protein - antagonists & inhibitors
rac1 GTP-Binding Protein - genetics
rac1 GTP-Binding Protein - metabolism
Rho GTPase
rhoA GTP-Binding Protein - genetics
rhoA GTP-Binding Protein - metabolism
RNA, Small Interfering - genetics
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2006.10.043