Overexpression of regulator of G protein signaling 11 promotes cell migration and associates with advanced stages and aggressiveness of lung adenocarcinoma
Autor: | Hsiu-Hsing Ko, Jr-Hau Lung, Neng-Yao Shih, Pei-Yi Chu, Wan-Wen Chen, Li-Tzong Chen, Chia-Hung Han, Sheng-Huei Yang, Chien-Feng Li |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine MAPK/ERK pathway Pathology medicine.medical_specialty Lung Neoplasms cell migration Cell Adenocarcinoma of Lung RAC1 Mice SCID Adenocarcinoma Transfection Mice 03 medical and health sciences 0302 clinical medicine Regulator of G protein signaling Downregulation and upregulation Cell Movement Mice Inbred NOD Cell Line Tumor Heterotrimeric G protein medicine Animals Humans Neoplasm Staging Paraffin Embedding business.industry RGS11 MAPK-FAK signalings Cell migration Middle Aged lung adenocarcinoma medicine.disease Survival Analysis Up-Regulation 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Heterografts Female business RGS Proteins Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | 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. |
Databáze: | OpenAIRE |
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