Abstract
Globally, hepatocellular carcinoma (HCC) is one of the most common causes of cancer-associated mortalities. It has a high rate of metastasis and recurrence, which predict a poor prognosis. G-protein-coupled receptor (GPCR)-kinase interacting protein-1 (GIT1) is a multifunctional scaffold protein that mediates the progression of various tumors. Studies have correlated GIT1 with HCC, however, these correlations have not been fully elucidated. Therefore, we aimed at evaluating the expression of GIT1 in HCC tissues and cells, and to investigate its role and potential mechanisms in HCC progression. The expression levels of GIT1 in HCC tissues and other cancers was determined by using the Oncomine and TCGA databases. Functional analysis of GIT1 in HCC was evaluated through in vitro and in vivo experiments, whereby, HCC cells were transfected with synthetically overexpressed and short hairpin RNA (shRNA) lentivirus-mediated plasmids. Kaplan-Meier and Cox regression methods were used to establish the associations between GIT1 and clinical outcomes of 158 HCC patients. GIT1 was found to be elevated in HCC tissues where it promoted the invasion, migration, and proliferation of HCC cells. Moreover, the overexpression of GIT1 prompted epithelial-mesenchymal transition (EMT) by activating extracellular regulated kinase 1/2 (ERK1/2) pathway, which was shown to be reversed by SCH772984, a specific ERK1/2 inhibitor. GIT1 was also found to be associated with malignant features of HCC, leading to a poorer prognosis. In conclusion, GIT1 promotes HCC progression by inducing EMT and may reflect the course of HCC patients.