Oncotarget

Research Papers:

Overexpression of regulator of G protein signaling 11 promotes cell migration and associates with advanced stages and aggressiveness of lung adenocarcinoma

Sheng-Huei Yang _, Chien-Feng Li, Pei-Yi Chu, Hsiu-Hsing Ko, Li-Tzong Chen, Wan-Wen Chen, Chia-Hung Han, Jr-Hau Lung and Neng-Yao Shih

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Oncotarget. 2016; 7:31122-31136. https://doi.org/10.18632/oncotarget.8860

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Abstract

Sheng-Huei Yang1,2, Chien-Feng Li2,3,*, Pei-Yi Chu2,4,*, Hsiu-Hsing Ko5,*, Li-Tzong Chen2,*, Wan-Wen Chen2, Chia-Hung Han2, Jr-Hau Lung6, Neng-Yao Shih2,7

1Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, Taiwan

2National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan

3Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan

4Department of Pathology, Show Chwan Memorial Hospital, Changhua City, Taiwan

5Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan

6Division of Pulmonary and Critical care Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan

7Graduate Institute of Medicine, College of Medicine, Kaoshiung Medical University, Kaoshiung, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Neng-Yao Shih, e-mail: [email protected]

Keywords: RGS11, cell migration, lung adenocarcinoma, MAPK-FAK signalings

Received: August 07, 2015     Accepted: April 01, 2016     Published: April 20, 2016

ABSTRACT

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.


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