Role of X‑linked inhibitor of apoptosis‑associated factor‑1 in vasculogenic mimicry in ovarian cancer.

Abstract

X-linked inhibitor of apoptosis‑associated factor1 (XAF1) was identified as a novel X-linked inhibitor of apoptosis (XIAP) binding partner that may reverse the anti‑apoptotic effect of XIAP. Previous studies have revealed that XAF1 serves an important role in cancer angiogenesis. Vasculogenic mimicry (VM) describes the formation of fluid‑conducting channels by highly invasive and genetically dysregulated tumor cells. VM is critical for tumor blood supply and is associated with aggressive actions and metastasis. The aim of present study was to investigate the potential association between XAF1 expression with VM of ovarian cancer, and evaluate the role of XAF1 in tumor cell migration and invasion of SKOV3 cells. VM structure and XAF1 expression were detected in 94 tissue samples of advanced epithelial ovarian cancer (EOC). Invasion and migration of the SKOV3 human ovarian carcinoma cell line were identified by Transwell assay. It was revealed that the presence of VM was associated with high grade advanced ovarian cancer. Reduced XAF1 expression was significantly associated with presence of VM. Overexpression of XAF1 significantly reduced invasion and migration of SKOV3 cells, and inhibited vascular endothelial growth factor protein expression. Furthermore, vasculature was suppressed by overexpression of XAF1 invivo in xenograft models. In conclusion, XAF1 expression was associated with VM in ovarian cancer, suggesting a potential role of XAF1 in the formation of VM in EOC. These findings may facilitate the development of novel therapeutic agents for the treatment of ovarian cancer.