Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/173542
Title: | HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis |
Author: | 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, Eduard Lázaro García, Conxi Flanagan, Adrienne M. Gorospe, Myriam Ratner, Nancy Aransay, Ana M. Carracedo, Arkaitz Varela Rey, Marta Woodhoo, Ashwin |
Keywords: | Cèl·lules canceroses Metàstasi Cancer cells Metastasis |
Issue Date: | 1-Jul-2020 |
Publisher: | American Society for Clinical Investigation Inc. |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1172/JCI130379 |
It is part of: | Journal of Clinical Investigation, 2020, vol. 130, num. 7, p. 3848-3864 |
URI: | http://hdl.handle.net/2445/173542 |
Related resource: | https://doi.org/10.1172/JCI130379 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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