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

Zhong-Zong Pan, Wendy Bruening, Andrew K Godwin
International Journal of Oncology 2006, 29 (5): 1201-5
Synuclein-gamma is aberrantly expressed in more than 70% of stage III/IV breast and ovarian carcinomas. Ectopic overexpression of synuclein-gamma enhanced MDA-MB-435 cell migration in vitro and metastasis in a nude mouse model. However, the mechanism of how synuclein-gamma promotes cell motility is not clear. In our previous studies, we showed that synuclein-gamma overexpression activates ERK. In the present study, we overexpressed synuclein-gamma in several breast and ovarian cancer cell lines and evaluated the effect of synuclein-gamma 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-gamma overexpressing cells. The ERK inhibitor U0126 also blocked the cell migration in both parental cells and synuclein-gamma overexpressing cells. Collectively, our data indicate that synuclein-gamma 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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"