Overexpression of regulator of G protein signaling 11 promotes cell migration and associates with advanced stages and aggressiveness of lung adenocarcinoma.
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.
Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan.|National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Sheng-Huei
SH
Yang
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.|Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.
Chien-Feng
CF
Li
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.|Department of Pathology, Show Chwan Memorial Hospital, Changhua City, Taiwan.
Pei-Yi
PY
Chu
Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.
Hsiu-Hsing
HH
Ko
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Li-Tzong
LT
Chen
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Wan-Wen
WW
Chen
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Chia-Hung
CH
Han
Division of Pulmonary and Critical care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Jr-Hau
JH
Lung
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaoshiung Medical University, Kaoshiung, Taiwan.
Neng-Yao
NY
Shih
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D020710:RGS Proteins / Q000096:biosynthesis* / Q000235:genetics; D016019:Survival Analysis; D014162:Transfection; D015854:Up-Regulation
D020710:RGS Proteins; C400195:RGS11 protein, human
MAPK-FAK signalings; RGS11; cell migration; lung adenocarcinoma