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 periphe...

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Authors: Palomo Irigoyen, Marta, Pérez Andrés, Encarni, Iruarrizaga Lejarreta, Marta, Barreira Manrique, Adrián, Tamayo Caro, Miguel, Vila Vecilla, Laura, Moreno Cugnon, Leire, Beitia, Nagore, Medrano, Daniela, Fernández Ramos, David, Lozano Salvatella, Juan José, Okawa, Satoshi, Lavín, José L., Martín Martín, Natalia, Sutherland, James D., Guitiérez de Juan, Virginia, González López, Monika, Macías Cámara, Nuria, Mosén Ansorena, David, Laraba, Liyam, Hanemann, C. Oliver, Ercolano, Emanuela, Parkinson, David B., Schultz, Christopher W., Araúzo Bravo, Marcos J., Ascensión, Alex M., Gerovska, Daniela, Iribar, Haizea, Izeta, Ander, Pytel, Peter, Krastel, Philipp, Provenzani, Alessandro, Seneci, Pierfausto, Carrasco, Ruben D., Sol, Antonio Del, Martínez Chantar, Maria Luz, Barrio, Rosa, Serra Arenas, Eduard, Lázaro García, Conxi, Flanagan, Adrienne M., Gorospe, Myriam, Ratner, Nancy, Aransay, Ana M., Carracedo, Arkaitz, Varela Rey, Marta, Woodhoo, Ashwin
Format: article
Status:Published version
Publication Date:2020
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/173542
Online Access:https://hdl.handle.net/2445/173542
Access Level:Open access
Keyword:Cèl·lules canceroses
Metàstasi
Cancer cells
Metastasis
Description
Summary: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.

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