Aim: Multiple studies have revealed that G-protein-coupled receptor kinase-interacting protein 1 (GIT1) is overexpressed in many cancers and facilitates tumor progression. However, the role of GIT1 in hepatocellular carcinoma (HCC) remains unclear.
Methods: GIT1 expression was detected in cell lines and 130 pairs of HCC and matched adjacent noncancerous samples. Transwell assay, flow cytometry, caspase 3/7 activity assay, 5-bromodeoxyuridine cell proliferation assay, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay were used to assess invasion, migration, apoptosis, and proliferation of HCC cells. Furthermore, GIT1 expression was detected by immunohistochemistry to evaluate its correlation with phospho-extracellular signal-regulated kinase (p-ERK)1/2. The regulatory effect of GIT1 on ERK1/2, p-ERK1/2, and matrix metalloproteinase-9 (MMP9) in HCC cells was confirmed by immunoblotting.
Results: In this study, we demonstrated that GIT1 was more highly expressed in HCC samples than that in non-HCC samples, and overexpression of GIT1 was correlated with clinicopathological features of poor prognosis. Clinical analysis demonstrated that GIT1 is an independent prognostic biomarker for predicting overall survival and disease-free survival of patients with HCC. In vitro studies showed that downregulation of GIT1 facilitated HCC cell apoptosis and repressed HCC cell invasion, migration, and proliferation. Overexpression of GIT1 is associated with p-ERK1/2 amplification in HCC tissues. Moreover, downregulation of GIT1 resulted in inactivation of ERK signaling and downregulation of MMP9.
Conclusion: Our findings indicate that GIT1 is an independent prognostic biomarker and facilitates HCC progression via activating ERK/MMP9 signaling.
Keywords: ERK signaling; GIT1; HCC; prognosis.