Zuo Yufeng, Shields Sarah-Kim, Chakraborty Chandan
Department of Pathology, Schulich School of Medicine and Dentistry, University of Western Ontario, Dental Sciences Building H422, London, ON, Canada N6A 5C1.
Biochem Biophys Res Commun. 2006 Dec 15;351(2):361-7. doi: 10.1016/j.bbrc.2006.10.043. Epub 2006 Oct 16.
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.
已知Rac GTP酶在调节细胞迁移所需的细胞骨架变化中起关键作用。在大多数细胞类型中，迁移已被证明受Rac正向调节。然而，在其他一些细胞类型中，关于Rac在迁移中的作用也存在大量相互矛盾的证据，这表明Rac GTP酶以细胞类型依赖的方式调节细胞迁移。在本研究中，我们已对Rac1 GTP酶抑制对多种具有不同程度致瘤和转移潜能的乳腺癌细胞系迁移能力的影响进行了表征。我们发现，在非转移性（MCF-7、T-47D）或中度转移性（Hs578T）细胞系中抑制Rac1会导致迁移受到抑制，而在高转移性细胞系（MDA-MB-435、MDA-MB-231和C3L5）中抑制Rac1会导致迁移受到刺激。Rac1抑制后迁移的这种刺激还伴随着RhoA活性增强，这表明在调节高转移性乳腺癌细胞的内在迁移中，RhoA可能对Rac1存在主导作用。
