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

Sanjeeb Kumar Sahu, Neha Tiwari, Abhijeet Pataskar, Yuan Zhuang, Marina Borisova, Mustafa Diken, Susanne Strand, Petra Beli and Vijay K. Tiwari ()
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Sanjeeb Kumar Sahu: Institute of Molecular Biology (IMB)
Neha Tiwari: University Medical Center, Johannes Gutenberg University
Abhijeet Pataskar: Institute of Molecular Biology (IMB)
Yuan Zhuang: Institute of Molecular Biology (IMB)
Marina Borisova: Institute of Molecular Biology (IMB)
Mustafa Diken: TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH
Susanne Strand: University Medical Center, Johannes Gutenberg University
Petra Beli: Institute of Molecular Biology (IMB)
Vijay K. Tiwari: Institute of Molecular Biology (IMB)

Nature Communications, 2017, vol. 8, issue 1, 1-18

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-01366-x

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