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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Commun 2017 ; 8 (ä): ä Nephropedia Template TP
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FBXO32 promotes microenvironment underlying epithelial-mesenchymal transition via CtBP1 during tumour metastasis and brain development #MMPMID29142217
Sahu SK; Tiwari N; Pataskar A; Zhuang Y; Borisova M; Diken M; Strand S; Beli P; Tiwari VK
Nat Commun 2017[]; 8 (ä): ä PMID29142217show ga
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.