TP53INP1 inhibits hypoxia-induced vasculogenic mimicry formation via the ROS/snail signalling axis in breast cancer.

Tumour protein p53-inducible nuclear protein 1 (TP53INP1) is a tumour suppressor associated with malignant tumour metastasis. Vasculogenic mimicry (VM) is a new tumour vascular supply pattern that significantly influences tumour metastasis and contributes to a poor prognosis. However, the molecular mechanism of the relationship between TP53INP1 and breast cancer VM formation is unknown. Here, we explored the underlying mechanism by which TP53INP1 regulates VM formation in vitro and in vivo. High TP53INP1 expression was not only negatively correlated with a poor prognosis but also had a negative relationship with VE-cadherin, HIF-1α and Snail expression. TP53INP1 overexpression inhibited breast cancer invasion, migration, epithelial-mesenchymal transition (EMT) and VM formation; conversely, TP53INP1 down-regulation promoted these processes in vitro by functional experiments and Western blot analysis. We established a hypoxia model induced by CoCl2 and assessed the effects of TP53INP1 on hypoxia-induced EMT and VM formation. In addition, we confirmed that a reactive oxygen species (ROS)-mediated signalling pathway participated in TP53INP1-mediated VM formation. Together, our results show that TP53INP1 inhibits hypoxia-induced EMT and VM formation via the ROS/GSK-3β/Snail pathway in breast cancer, which offers new insights into breast cancer clinical therapy.