Supervillin promotes tumor angiogenesis in liver cancer
Chenggang Zhao, Zhiyang Zhao, Zhen Wang, Lizhu Hu, Hongzhi Wang, Zhiyou Fang
Abstract
Tumor angiogenesis is a hallmark of liver cancer and is necessary for tumor growth and progression. Supervillin (SVIL) is highly expressed and implicated in several malignant processes of liver cancer. However, the functional relationships between SVIL and tumor angiogenesis in liver cancer have not yet been fully elucidated. The present study was based on bioinformatics analysis, patient tissue sample detection, three‑dimensional simulated blood vessel formation, a series of cytological experiments and mouse models. The results demonstrated the important role of SVIL in the progression of malignant liver cancer and tumor angiogenesis, both in terms of vasculogenic mimicry (VM) and endothelium‑dependent vessel (EDV) development. SVIL knockdown inhibited VM formation and induced tumor cell apoptosis via the VEGF‑p38 signaling axis and through various VM‑associated transcriptional factors, including vascular endothelial‑cadherin, matrix metalloproteinase 9/12 and migration‑inducing protein 7. SVIL may therefore be considered a potential tumor vascular biomarker and a promising therapeutic target for patients with liver cancer.