YY1 Promotes Endothelial Cell-Dependent Tumor Angiogenesis in Hepatocellular Carcinoma by Transcriptionally Activating VEGFA

Autor: Wendong Yang, Zhongwei Li, Rong Qin, Xiaorui Wang, Huihui An, Yule Wang, Yan Zhu, Yantao Liu, Shijiao Cai, Shuang Chen, Tao Sun, Jing Meng, Cheng Yang
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Frontiers in Oncology, Vol 9 (2019)
Druh dokumentu: article
ISSN: 2234-943X
DOI: 10.3389/fonc.2019.01187
Popis: Hepatocellular carcinoma (HCC) is a typical hypervascular solid tumor that requires neoangiogenesis for growth. The vascular endothelial growth factor (VEGF) is the most potent proangiogenic factor in neovascularization. The multifunctional Yin-Yang 1 (YY1) is involved in the regulation of tumor malignancy of HCC. However, the relationship between YY1 and endothelial cell-dependent tumor angiogenesis in HCC remains unclear. In this study, we observed that YY1 is positively correlated with microvessel density (MVD) and poor prognosis in HCC tissues. We further found that YY1 promotes the transcriptional activity of VEGFA by binding its promoter in HCC. The secreted VEGFA from HCC cells activates phosphorylation of VEGFR2 to promotes tube formation, cell migration, and invasion of vascular endothelial cells in vitro, and promotes tumor growth and angiogenesis in vivo. In addition, upregulation of YY1 enhanced resistance of bevacizumab in HCC cells. These results indicate that YY1 plays essential roles in HCC angiogenesis and resistance of bevacizumab by inducing VEGFA transcription and that YY1 may represent a potential molecular target for antiangiogenic therapy during HCC progression.
Databáze: Directory of Open Access Journals