title: GIT1 is a novel prognostic biomarker and facilitates tumor progression via activating ERK/MMP9 signaling in hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our findings indicate that GIT1 is an independent prognostic biomarker and facilitates HCC progression via activating ERK/MMP9 signaling.
authors.affiliation: Department of General Surgery, Branch of the First People's Hospital of Shanghai, People's Republic of China.
authors.forename: Junyi
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Hepatic Surgery, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, People's Republic of China.
authors.forename: Pinghua
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Hepatic Surgery, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, People's Republic of China.
authors.forename: Jue
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Hepatic Surgery, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, People's Republic of China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Hepatic Surgery, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, People's Republic of China.
authors.forename: Baohua
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Branch of the First People's Hospital of Shanghai, People's Republic of China ; Department of Traditional Chinese Medicine, Branch of the first People's Hospital of Shanghai, Shanghai, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
keywords: ERK signaling; GIT1; HCC; prognosis