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, Vijay K. Tiwari

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)
175 Downloads (Pure)

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. Epithelial-to-mesenchymal transition (EMT) regulates both processes of organism development and changes in cell state causing disease. Here, the authors show that an E3 ubiquitin ligase, FBXO32, regulates EMT via CtBP1 and the transcriptional program, and also mediates cancer metastatic burden and neurogenesis.
Original languageEnglish
JournalNature Communications
Volume8
Issue number1
Early online date17 Nov 2017
DOIs
Publication statusPublished - 01 Dec 2017

Fingerprint Dive into the research topics of 'FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development'. Together they form a unique fingerprint.

Cite this