Inhibiting GIT1 reduces the growth, invasion, and angiogenesis of osteosarcoma

Cancer Management and Research. 2018;Volume 10:6445-6455

 

Journal Homepage

Journal Title: Cancer Management and Research

ISSN: 1179-1322 (Online)

Publisher: Dove Medical Press

LCC Subject Category: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens

Country of publisher: United Kingdom

Language of fulltext: English

Full-text formats available: PDF, HTML

 

AUTHORS

Zhang Z
Hu P
Xiong J
Wang S

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 16 weeks

 

Abstract | Full Text

Zitao Zhang,1 Polu Hu,2 Jin Xiong,1 Shoufeng Wang1 1Department of Orthopedics, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China; 2Nanjing Red Cross Blood Center, Nanjing 210003, China Background: GIT1, a scaffold protein with ubiquitous multi-domain, is involved in many cellular processes. In recent years, it was proved that GIT1 participated in various tumors’ growth or metastasis. However, the biological function of GIT1 in osteosarcoma is still unclear. In this study, we aimed to investigate the role and mechanism of GIT1 in osteosarcoma.Materials and methods: Human osteosarcoma tissues were obtained to investigate the distribution of GIT1. Adequate osteosarcoma cells were stably infected with lentivirus to knockdown GIT1 level and then was used to carry out cell invasion and vascular endothelial growth factor (VEGF) assay in vitro. Orthotopic femoral osteosarcoma model was constructed to investigate the growth, invasion, and angiogenesis in vivo. Western blot was used to detect extracellular signal-regulated kinase (ERK1/2) activation and hypoxia-inducible factor-1 (HIF-1α) expression.Results: In this study, we found that GIT1 was distributed in human osteosarcoma tissues and highly expressed in osteosarcoma (OS) cells. Knockdown of GIT1 inhibited cell invasion and VEGF release in vitro and suppressed tumor growth, invasion, and angiogenesis in vivo. Furthermore, knockdown of GIT1 substantially downregulated the protein levels of p-ERK and HIF-1α in OST cells and inhibition of p-ERK by PD98059 could significantly decrease the expression of HIF-1α and concentration of VEGF in GIT1-shRNA-treated cells.Conclusion: GIT1 knockdown can effectively inhibit the growth, invasion, and angiogenesis of osteosarcoma. Thus, GIT1 might act as an oncogenic factor in osteosarcoma and could be a potential molecular target for osteosarcoma gene therapy. Keywords: GIT1, osteosarcoma, angiogenesis, orthotopic femoral osteosarcoma model, ERK1/2, HIF-1α