VBP1 represses cancer metastasis by enhancing HIF‐1α degradation induced by pVHL

von Hippel‐Lindau‐binding protein 1 (VBP1) physically interacts with pVHL, an E3‐ubiquitin ligase, which degrades HIF‐1α in an oxygen‐dependent manner. HIF‐1 is a key regulator of adaptive responses to a lack of oxygen that controls glucose metabolism, angiogenesis, proliferation, invasion, and metastasis. However, the role of VBP1 in pVHL‐mediated degradation of HIF‐1α is not yet known. In this study, we show that VBP1 enhances the stability of pVHL and facilitates pVHL‐mediated ubiquitination of HIF‐1α. Furthermore, VBP1 suppresses HIF‐1α‐induced epithelial‐mesenchymal transition in vitro and tumor metastasis in vivo. These findings suggest that VBP1 is a bona fide tumor suppressor protein associated with HIF‐1α regulation. von Hippel‐Lindau‐binding protein 1 (VBP1) physically interacts with von Hippel‐Lindau protein (pVHL). However, the role of VBP1 in pVHL‐mediated degradation of hypoxia‐inducible factor 1α (HIF‐1α) is not elucidated yet. Here, we report that VBP1 enhances pVHL stability and facilitates pVHL‐mediated ubiquitination and degradation of HIF‐1α. Furthermore, VBP1 suppresses HIF‐1α‐induced epithelial–mesenchymal transition in vitro and tumor metastasis in vivo.