Autor: |
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 |
Jazyk: |
angličtina |
Rok vydání: |
2021 |
Předmět: |
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Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 23, Iss , Pp 797-810 (2021) |
Druh dokumentu: |
article |
ISSN: |
2162-2531 |
DOI: |
10.1016/j.omtn.2021.01.001 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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