Involvement of RHO GTPases and ERK in synuclein-γ enhanced cancer cell motility

  • Authors:
    • Zhong-Zong Pan
    • Wendy Bruening
    • Andrew K. Godwin
  • View Affiliations

  • Published online on: November 1, 2006     https://doi.org/10.3892/ijo.29.5.1201
  • Pages: 1201-1205
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Abstract

Synuclein-γ is aberrantly expressed in more than 70% of stage III/IV breast and ovarian carcinomas. Ectopic overexpression of synuclein-γ enhanced MDA-MB-435 cell migration in vitro and metastasis in a nude mouse model. However, the mechanism of how synuclein-γ promotes cell motility is not clear. In our previous studies, we showed that synuclein-γ overexpression activates ERK. In the present study, we overexpressed synuclein-γ in several breast and ovarian cancer cell lines and evaluated the effect of synuclein-γ on the activity of small G-protein RHO family members. We found that at least one of the RHO/RAC/CDC42 GTPases showed a higher level of the GTP-bound active form. Consistent with their role in regulating the intracellular motile machinery, inhibition of the RHO/RAC/CDC42 by C. difficile Toxin B blocked cell migration in both parental cells and synuclein-γ overexpressing cells. The ERK inhibitor U0126 also blocked the cell migration in both parental cells and synuclein-γ overexpressing cells. Collectively, our data indicate that synuclein-γ might be involved in late stage breast and ovarian cancer metastasis by enhancing cell motility through activation of the RHO family small-GTPases and ERK.

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November 2006
Volume 29 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Pan Z, Bruening W and Godwin AK: Involvement of RHO GTPases and ERK in synuclein-γ enhanced cancer cell motility. Int J Oncol 29: 1201-1205, 2006
APA
Pan, Z., Bruening, W., & Godwin, A.K. (2006). Involvement of RHO GTPases and ERK in synuclein-γ enhanced cancer cell motility. International Journal of Oncology, 29, 1201-1205. https://doi.org/10.3892/ijo.29.5.1201
MLA
Pan, Z., Bruening, W., Godwin, A. K."Involvement of RHO GTPases and ERK in synuclein-γ enhanced cancer cell motility". International Journal of Oncology 29.5 (2006): 1201-1205.
Chicago
Pan, Z., Bruening, W., Godwin, A. K."Involvement of RHO GTPases and ERK in synuclein-γ enhanced cancer cell motility". International Journal of Oncology 29, no. 5 (2006): 1201-1205. https://doi.org/10.3892/ijo.29.5.1201