HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis.
Cancer
Cell Biology
Epigenetics
Oncogenes
Oncology
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
20
05
2019
accepted:
14
04
2020
pubmed:
22
4
2020
medline:
3
2
2021
entrez:
22
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32315290
pii: 130379
doi: 10.1172/JCI130379
pmc: PMC7324187
doi:
pii:
Substances chimiques
ELAV-Like Protein 1
0
ELAVL1 protein, human
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3848-3864Références
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