Regulator of
G protein signaling 11 (RGS11), a member of the R7 subfamily of
RGS proteins, is a well-characterized
GTPase-accelerating
protein that is involved in the
heterotrimeric G protein regulation of the amplitude and kinetics of receptor-promoted signaling in
retinal bipolar and nerve cells. However, the role of RGS11 in
cancer is completely unclear. Using subtractive hybridization analysis, we found that RGS11 was highly expressed in the lymph-node metastatic tissues and bone-metastatic
tumors obtained from patients with
lung adenocarcinoma. Characterization of the clinicopathological features of 91 patients showed that around 57.1% of the
tumor samples displayed RGS11 overexpression that was associated with primary
tumor status, nodal
metastasis and increased disease stages. Its high expression was an independent predictive factor for poor prognosis of these patients. Cotransfection of
guanine nucleotide-
binding protein beta-5 (GNB5) markedly increased RGS11 expression. Enhancement or attenuation of RGS11 expression pinpointed its specific role in cell migration, but not in cell invasion and proliferation. Signaling events initiated by the RGS11-GNB5 coexpression activated the c-Raf/ERK/FAK-mediated pathway through upregulation of the Rac1 activity. Consistently, increasing the cell invasiveness of the transfectants by additional cotransfection of the exogenous
urokinase-
plasminogen activator gene caused a significant promotion in cell invasion in vitro and in vivo, confirming that RGS11 functions in cell migration, but requires additional proteolytic activity for cell and tissue invasion. Collectively, overexpression of RGS11 promotes cell migration, participates in
tumor metastasis, and correlates the clinicopathological conditions of patients with
lung adenocarcinoma.