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Aggressive tumor cells can mimic embryonic vasculogenic networks and form vasculogenic mimicry (VM). Preliminary studies demonstrated that hypoxia can promote VM formation; however, the underlying mechanism remains unclear. The present study aimed to investigate the role of the Twist1‑Bmi1 connection in hypoxia‑induced VM formation and the underlying mechanism. In the in vitro experiments, western blot analysis demonstrated that hypoxia upregulated the expression of Twist1, Bmi1, epithelial‑mesenchymal transition (EMT) markers, stem cell markers and VM‑associated markers. The 3D culture assay showed that hypoxia promoted VM formation in hepatocellular carcinoma (HCC) cell lines. Using transfection and in vitro cell experiments, the Twist1‑Bmi1 connection was confirmed to have an important role in inducing EMT, cell stemness and VM formation. In the in vivo experiments, the murine hypoxia models were established via incomplete femoral artery ligation and the mechanism by which hypoxia promoted Twist1 and Bmi1 expression and led to VM formation was demonstrated by immunohistochemistry staining and endomucin/periodic acid Schiff double‑staining. In conclusion, hypoxia upregulate the expression of Twist1 and Bmi1, and these two proteins have an important role in inducing EMT and cancer cell stemness, which contributed to VM formation.

Transcription factor Slug plays an important role in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). This study aimed to explore the mechanism involved in the promotion of HCC progression by Slug. In the precent study, we demonstrated that Slug expression was significantly associated with metastasis and shorter survival time of HCC patients. Using ChIP-on-chip and microarray analysis, we identified the molecular profile of Slug downstream targets in HCC cells with Slug overexpression. The Wnt, Notch and Hedgehog pathways were identified to promote pluripotency maintaining overexpression factors sox2 and nanog. Importantly, Slug showed a close relationship with sox2 and nanog expression in HCC patients and in HCC xenografts in vivo. Notably, the DNA damaging reagent hydroxyurea had no effect on Slug, sox2 and nanog expression in HCC cells with Slug overexpression; however knockdown of Slug by the short hairpin RNA approach markedly reduced sox2 and nanog expression and inhibited HCC cell migration in vitro. The results of this study indicate that Slug promotes progression of HCC by promoting sox2 and nanog overexpression. The related molecular pathways may be used as novel therapeutic targets for HCC.