GRK5 promotes tumor progression in renal cell carcinoma

Tang-Liang Zhao, Xin-Xin Gan, Yi Bao, Wei-Ping Wang, Bing Liu,  Lin-Hui Wang

Abstract:

GRK5 is a multifunctional protein that is able to move within the cell in response to various stimuli to regulate key intracellular signaling from receptor activation on plasma membrane to gene transcription in the nucleus. Thus, GRK5 is involved in the development and progression of several pathological conditions including cancer. Here, we report an important tumor-promoting role for GRK5 in renal cell carcinoma (RCC). We investigated the expression pattern, clinical significance, and function of GRK5 in RCC. By using quantitative real-time polymerase chain reaction (qRT-PCR) and tissue microarray (TMA) immunohistochemistry (IHC), we first demonstrated that compared to the paired adjacent non-tumor (NT) tissues, RCC tissues presented with higher GRK5 expression. Moreover, we found that GRK5 upregulation was associated with poor clinical outcomes in RCC patients. In vitro, we found that GRK5 knockdown reduced viability, invasive ability, migratory ability, and decreased proportion of cells in S phase with concomitant increase in G1 phase in RCC cell lines, while GRK5 overexpression promoted tumor cell proliferation, cell invasion, migration and increased proportion of cells in S phase with concomitant decrease in G1 phase. Collectively, our findings describe a tumor-promoting role of GRK5 in RCC and thus provide molecular evidence for new therapeutic options in RCC.