OncoTargets and Therapy (May 2021)
Gαi1 Promoted Proliferation, Migration and Invasion via Activating the Akt-mTOR/Erk-MAPK Signaling Pathway in Renal Cell Carcinoma
Abstract
Zhan Chen,1,2,* Yong Zhang,1,2,* Xiang Wu,1 Ji Zhang,1 Wei Xu,1,2 Cheng Shen,1,2 Bing Zheng1 1Department of Urology, The Second Affiliated Hospital of Nantong University, Nantong, People’s Republic of China; 2Medical Research Center, The Second Affiliated Hospital of Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing ZhengDepartment of Urology, The Second Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of ChinaTel +86-13813605988Email [email protected]: Renal cell carcinoma (RCC) accounts for about 2– 3% of all adult malignancies. G protein alpha inhibitory subunit 1 (Gαi1) plays a key role in mediating PI3K-Akt signaling upon activation of receptor tyrosine kinases (RTKs). However, little is known about its expression, regulation and biological function in RCC.Methods: Gαi1 expression in RCC tissues and cells was detected by quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry (IHC). The effect of Gαi1 silence on cell proliferation and apoptosis of 786-O and ACHN cells was detected by CCK-8 assay and flow cytometry. Wound-healing assay and Transwell assays were used to detect the cell invasion in RCC cells. The expression of CDK4, cyclin D1, MMP-2, MMP-9, Bax, Bcl-2, p/t-Akt, p/t-S6 and p/t-Erk was detected by Western blot and qRT-PCR. Furthermore, a nude mouse subcutaneous xenograft model was used to further evaluate the potential effects of Gail in vivo.Results: In the present study, our data showed that Gαi1 expression was dramatically increased in RCC tissues compared with normal renal tissues. In addition, knocking down the expression of Gαi1 subsequently inhibited proliferation, migration and invasion of RCC cells in vivo and vitro. Furthermore, the expression of CDK4, cyclin D1, MMP-2 and MMP-9 was significantly reduced upon Gαi1 inhibition. Gαi1 positively regulates the activation of the mTOR and Erk pathways.Conclusion: In conclusion, this study reveals Gαi1 promoted proliferation via activating the Akt-mTOR and Erk-MAPK signaling pathways in RCC, and Gαi1 may be a therapeutic and prognostic target for RCC.Keywords: renal cell carcinoma, Gαi1, cell proliferation, cell migration, therapeutic targets
