Inhibiting GIT1 reduces the growth, invasion, and angiogenesis of osteosarcoma
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...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-11-01
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| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/inhibiting-git1-reduces-the-growth-invasion-and-angiogenesis-of-osteos-peer-reviewed-article-CMAR |
| _version_ | 1828496893687103488 |
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| author | Zhang Z Hu P Xiong J Wang S |
| author_facet | Zhang Z Hu P Xiong J Wang S |
| author_sort | Zhang Z |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-11T12:37:51Z |
| format | Article |
| id | doaj.art-219e44eaf70b4187afc324b763e8e83f |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-11T12:37:51Z |
| publishDate | 2018-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-219e44eaf70b4187afc324b763e8e83f2022-12-22T01:07:03ZengDove Medical PressCancer Management and Research1179-13222018-11-01Volume 106445645542731Inhibiting GIT1 reduces the growth, invasion, and angiogenesis of osteosarcomaZhang ZHu PXiong JWang SZitao 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-1αhttps://www.dovepress.com/inhibiting-git1-reduces-the-growth-invasion-and-angiogenesis-of-osteos-peer-reviewed-article-CMARGIT1osteosarcomaangiogenesisorthotopic femoral osterosarcoma modelERK1/2HIF-1α |
| spellingShingle | Zhang Z Hu P Xiong J Wang S Inhibiting GIT1 reduces the growth, invasion, and angiogenesis of osteosarcoma Cancer Management and Research GIT1 osteosarcoma angiogenesis orthotopic femoral osterosarcoma model ERK1/2 HIF-1α |
| title | Inhibiting GIT1 reduces the growth, invasion, and angiogenesis of osteosarcoma |
| title_full | Inhibiting GIT1 reduces the growth, invasion, and angiogenesis of osteosarcoma |
| title_fullStr | Inhibiting GIT1 reduces the growth, invasion, and angiogenesis of osteosarcoma |
| title_full_unstemmed | Inhibiting GIT1 reduces the growth, invasion, and angiogenesis of osteosarcoma |
| title_short | Inhibiting GIT1 reduces the growth, invasion, and angiogenesis of osteosarcoma |
| title_sort | inhibiting git1 reduces the growth invasion and angiogenesis of osteosarcoma |
| topic | GIT1 osteosarcoma angiogenesis orthotopic femoral osterosarcoma model ERK1/2 HIF-1α |
| url | https://www.dovepress.com/inhibiting-git1-reduces-the-growth-invasion-and-angiogenesis-of-osteos-peer-reviewed-article-CMAR |
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