Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 130, Issue 7, Pages 3848-3864Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI130379
Keywords
-
Categories
Funding
- Spanish Association Against Cancer (AECC)
- Spanish Ministry of Science, Innovation and Universities (MCIU)/Agencia Estatal de Investigacion (AEI)/European Regional Development Fund (FEDER), European Union (EU) [RYC2010-06901, RTI2018-097503-B-I00, SAF2015-65360-R, SAF2015-72416-EXP, SAF2015-62588-ERC]
- BBVA Foundation
- Basque Department of Industry, Tourism and Trade (Elkartek)
- Basque Department of Education [PI2013-46, IKERTALDE IT1106-16]
- Fundacion Vasca de Innovacion e Investigacion Sanitarias EiTB Maratoia [BIO13/CI/015]
- Neurofibromatosis Therapeutic Acceleration Program
- European Research Council (EU's Horizon 2020 research and innovation programme) [865157]
- 2017 Leonardo Grant for Researchers and Cultural Creators (BBVA Foundation)
- Accion Estrategica Ciber Emergentes 2018 (Ciberehd-ISCIII)
- Gilead Sciences International Research Scholars Program in Liver Disease
- MCIU/AEI [SAF2016-79381-R, SEV-2016-0644, SAF20168-1975-REDT]
- European Training Networks Project [H2020-MSCA-ITN-308 2016 721532]
- AECC [IDEAS175CARR, GCTRA18006CARR]
- European Research Council [336343, PoC 754627]
- Basque Government of Education fellowship
- Ayudas para contratos predoctorales para la formacion de doctores (MCIU/AEI/FEDER, EU)
- Brain Tumour Research
- MCIU/AEI/FEDER, EU [BFU2014-52282-P, BFU2017-84653-P, SAF2017-87301-R]
- Carlos III National Health Institute - FEDER funds - a way to build Europe (CIBERONC)
- Government of Catalonia [2017SGR496]
- Asociacion Espanola Contra El Cancer (AECC)
- AECC Canceres Raros
- BBVA Biomedicina (UMBRELLA)
- La CAIXA Foundation [LCF/PR/HP17/52190004]
- Associazione Italiana Ricerca sul Cancro (AIRC) [21548]
- Instituto de Salud Carlos III
- MCIU [SEV-2016-0644]
- Intramural Research Program of the National Institute on Aging, NIH
- NATIONAL INSTITUTE ON AGING [ZIAAG000518, ZIAAG000511] Funding Source: NIH RePORTER
- European Research Council (ERC) [865157] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
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/beta-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available