LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis in ICC
Aberrant expression of lysyl oxidase-like 1 (LOXL1) reportedly leads to fibrous diseases. Recent studies have revealed its role in cancers. In this study, we observed an elevated level of LOXL1 in the tissues and sera of patients with intrahepatic cholangiocarcinoma (ICC) compared with levels in non...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253121000019 |
| _version_ | 1818616643000991744 |
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| author | Ruiyan Yuan Yang Li Bo Yang Zhaohui Jin Jiacheng Xu Ziyu Shao Huijie Miao Tai Ren Yang Yang Guoqiang Li Xiaoling Song Yunping Hu Xu’an Wang Ying Huang Yingbin Liu |
| author_facet | Ruiyan Yuan Yang Li Bo Yang Zhaohui Jin Jiacheng Xu Ziyu Shao Huijie Miao Tai Ren Yang Yang Guoqiang Li Xiaoling Song Yunping Hu Xu’an Wang Ying Huang Yingbin Liu |
| author_sort | Ruiyan Yuan |
| collection | DOAJ |
| description | Aberrant expression of lysyl oxidase-like 1 (LOXL1) reportedly leads to fibrous diseases. Recent studies have revealed its role in cancers. In this study, we observed an elevated level of LOXL1 in the tissues and sera of patients with intrahepatic cholangiocarcinoma (ICC) compared with levels in nontumor tissues and sera of unaffected individuals. Overexpression of LOXL1 in RBE and 9810 cell lines promoted cell proliferation, colony formation, and metastasis in vivo and in vitro and induced angiogenesis. In contrast, depletion of LOXL1 showed the opposite effects. We further showed that LOXL1 interacted with fibulin 5 (FBLN5), which regulates angiogenesis, through binding to the αvβ3 integrin in an arginine-glycine-aspartic (Arg-Gly-Asp) domain-dependent mechanism and enhanced the focal adhesion kinase (FAK)-mitogen-activated protein kinase (MAPK) signaling pathway inside vascular endothelial cells. Our findings shed light on the molecular mechanism underlying LOXL1 regulation of angiogenesis in ICC development and indicate that the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis might be the critical pathological link leading to angiogenesis in ICC. |
| first_indexed | 2024-12-16T16:53:03Z |
| format | Article |
| id | doaj.art-a1847a6aa2f1499fac7047d5e3741897 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-16T16:53:03Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-a1847a6aa2f1499fac7047d5e37418972022-12-21T22:23:58ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-03-0123797810LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis in ICCRuiyan Yuan0Yang Li1Bo Yang2Zhaohui Jin3Jiacheng Xu4Ziyu Shao5Huijie Miao6Tai Ren7Yang Yang8Guoqiang Li9Xiaoling Song10Yunping Hu11Xu’an Wang12Ying Huang13Yingbin Liu14State Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaState Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Department of Surgery, First Affiliated Hospital of Wenzhou Medical University, Baixiang Road, Wenzhou 325000, ChinaState Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, ChinaState Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaState Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaState Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaState Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaState Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaState Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaState Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaDepartment of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China; Corresponding author: Xu’an Wang, Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China.State Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Corresponding author: Ying Huang, State Key Laboratory of Oncogenes and Related Genes, Department of General Surgery, Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China; Corresponding author: Yingbin Liu, Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China.Aberrant expression of lysyl oxidase-like 1 (LOXL1) reportedly leads to fibrous diseases. Recent studies have revealed its role in cancers. In this study, we observed an elevated level of LOXL1 in the tissues and sera of patients with intrahepatic cholangiocarcinoma (ICC) compared with levels in nontumor tissues and sera of unaffected individuals. Overexpression of LOXL1 in RBE and 9810 cell lines promoted cell proliferation, colony formation, and metastasis in vivo and in vitro and induced angiogenesis. In contrast, depletion of LOXL1 showed the opposite effects. We further showed that LOXL1 interacted with fibulin 5 (FBLN5), which regulates angiogenesis, through binding to the αvβ3 integrin in an arginine-glycine-aspartic (Arg-Gly-Asp) domain-dependent mechanism and enhanced the focal adhesion kinase (FAK)-mitogen-activated protein kinase (MAPK) signaling pathway inside vascular endothelial cells. Our findings shed light on the molecular mechanism underlying LOXL1 regulation of angiogenesis in ICC development and indicate that the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis might be the critical pathological link leading to angiogenesis in ICC.http://www.sciencedirect.com/science/article/pii/S2162253121000019angiogenesisintrahepatic cholangiocarcinomalysyl oxidase-like 1vascular endothelial celltumorigenesisLOXL1 |
| spellingShingle | Ruiyan Yuan Yang Li Bo Yang Zhaohui Jin Jiacheng Xu Ziyu Shao Huijie Miao Tai Ren Yang Yang Guoqiang Li Xiaoling Song Yunping Hu Xu’an Wang Ying Huang Yingbin Liu LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis in ICC Molecular Therapy: Nucleic Acids angiogenesis intrahepatic cholangiocarcinoma lysyl oxidase-like 1 vascular endothelial cell tumorigenesis LOXL1 |
| title | LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis in ICC |
| title_full | LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis in ICC |
| title_fullStr | LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis in ICC |
| title_full_unstemmed | LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis in ICC |
| title_short | LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis in ICC |
| title_sort | loxl1 exerts oncogenesis and stimulates angiogenesis through the loxl1 fbln5 αvβ3 integrin fak mapk axis in icc |
| topic | angiogenesis intrahepatic cholangiocarcinoma lysyl oxidase-like 1 vascular endothelial cell tumorigenesis LOXL1 |
| url | http://www.sciencedirect.com/science/article/pii/S2162253121000019 |
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