FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development

Nat Commun. 2017 Nov 15;8(1):1523. doi: 10.1038/s41467-017-01366-x.


The set of events that convert adherent epithelial cells into migratory cells are collectively known as epithelial-mesenchymal transition (EMT). EMT is involved during development, for example, in triggering neural crest migration, and in pathogenesis such as metastasis. Here we discover FBXO32, an E3 ubiquitin ligase, to be critical for hallmark gene expression and phenotypic changes underlying EMT. Interestingly, FBXO32 directly ubiquitinates CtBP1, which is required for its stability and nuclear retention. This is essential for epigenetic remodeling and transcriptional induction of CtBP1 target genes, which create a suitable microenvironment for EMT progression. FBXO32 is also amplified in metastatic cancers and its depletion in a NSG mouse xenograft model inhibits tumor growth and metastasis. In addition, FBXO32 is essential for neuronal EMT during brain development. Together, these findings establish that FBXO32 acts as an upstream regulator of EMT by governing the gene expression program underlying this process during development and disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / genetics*
  • Alcohol Oxidoreductases / metabolism
  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Cell Line, Tumor
  • Cells, Cultured
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • Neoplasm Metastasis
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • RNA Interference
  • SKP Cullin F-Box Protein Ligases / genetics*
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Transplantation, Heterologous
  • Tumor Microenvironment / genetics*


  • DNA-Binding Proteins
  • Muscle Proteins
  • Alcohol Oxidoreductases
  • C-terminal binding protein
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases