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

FEBS J. 2018 Jan;285(1):115-126. doi: 10.1111/febs.14322. Epub 2017 Dec 12.

Abstract

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.

Keywords: EMT; pVHL; HIF-1α; VBP1; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Cytoskeletal Proteins
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Mice, Inbred C57BL
  • Molecular Chaperones
  • Neoplasm Metastasis
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Protein Binding
  • RNA Interference
  • Ubiquitination
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism*

Substances

  • Carrier Proteins
  • Cytoskeletal Proteins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Molecular Chaperones
  • VBP1 protein, human
  • Von Hippel-Lindau Tumor Suppressor Protein
  • VHL protein, human