HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis

Cancer cells can develop a strong addiction to discrete molecular regulators, which control the aberrant gene expression programs that drive and maintain the cancer phenotype. Here, we report the identification of the RNA-binding protein HuR/ELAVL1 as a central oncogenic driver for malignant peripheral nerve sheath tumors (MPNSTs), which are highly aggressive sarcomas that originate from cells of the Schwann cell lineage. HuR was found to be highly elevated and bound to a multitude of cancer-associated transcripts in human MPNST samples. Accordingly, genetic and pharmacological inhibition of HuR had potent cytostatic and cytotoxic effects on tumor growth, and strongly suppressed metastatic capacity in vivo. Importantly, we linked the profound tumorigenic function of HuR to its ability to simultaneously regulate multiple essential oncogenic pathways in MPNST cells, including the Wnt/β-catenin, YAP/TAZ, RB/E2F, and BET pathways, which converge on key transcriptional networks. Given the exceptional dependency of MPNST cells on HuR for survival, proliferation, and dissemination, we propose that HuR represents a promising therapeutic target for MPNST treatment

Tet3 loss of function results in metabolic abnormalities in the intestinal epithelium

Póster presentado a: Metabolism meets epigenetics Virtual, 17-23 de noviembre de 20215hmC is an epigenetic modification with differential spatial distribution in the small intestinal epithelium. A. TET proteins (TET1, TET2 and TET3) are able to oxydize 5mC into 5hmC which can function as an stable epigenetic mark or as an intermediate during active demethylation. 5hmC associates with the activation of key genes during cellular differentiation. B. Organization of the intervillusvillus axis in the mouse neonatal small intestinal epithelium and 5hmC distribution. 5hmC is gradually deposited at the DNA of cells as they migrate towards the villus tip.C, cytosine; 5mC, 5-methylcytosine; 5hmC, 5-hydroxymethylcytosine; 5fC, 5-formylcytosine; 5caC, 5-carboxylcytosine; DNMTs, DNA methyltransferases; TETs, ten-eleven translocation; BER, base-excision repair.Ministerio de Economía y EmpresaPeer reviewe