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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Detalles Bibliográficos
Autores: 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, Juan José, Okawa, Satoshi, Lavín, José L., Martín Martín, Natalia, Sutherland, James D., Gutiérez 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 López, Haizea, Izeta Permisán, Ander, Pytel, Peter, Krastel, Philipp, Provenzani, Alessandro, Seneci, Pierfausto, Carrasco, Ruben D., Del Sol, Antonio, Martínez Chantar, María Luz, Barrio Olano, María Rosa, Serra, Eduard, Lazaro, Conxi, Flanagan, Adrienne M., Gorospe, Myriam, Ratner, Nancy, Aransay Bañares, Ana María, Carracedo Pérez, Arkaitz, Varela Rey, Marta, Woodhoo, Ashwin
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/50014
Acceso en línea:http://hdl.handle.net/10810/50014
Access Level:acceso abierto
Palabra clave:RNA-binding proteins
aurora kinase
enrichment analysis
schwann-cells
RIP-chip
cancer
target
identification
transcription
inhibition
Descripción
Sumario: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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