دورية أكاديمية
HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis
| العنوان: | HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis |
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| المؤلفون: | 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., de Juan, Virginia Guitiérez, Gonzalez-Lopez, 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., Del Sol, Antonio, Martinez-Chantar, María Luz, Barrio, Rosa, Serra, Eduard, Lazaro, Conxi, Flanagan, Adrienne M., Gorospe, Myriam, Ratner, Nancy, Aransay, Ana M., Carracedo, Arkaitz, Varela-Rey, Marta, Woodhoo, Ashwin |
| المساهمون: | M. Palomo-Irigoyen, E. Pérez-André, M. Iruarrizaga-Lejarreta, A. Barreira-Manrique, M. Tamayo-Caro, L. Vila-Vecilla, L. Moreno-Cugnon, N. Beitia, D. Medrano, D. Fernández-Ramo, J.J. Lozano, S. Okawa, J.L. Lavín, N. Martín-Martín, J.D. Sutherland, V.G. de Juan, M. Gonzalez-Lopez, N. Macías-Cámara, D. Mosén-Ansorena, L. Laraba, C.O. Hanemann, E. Ercolano, D.B. Parkinson, C.W. Schultz, M.J. Araúzo-Bravo, A.M. Ascensión, D. Gerovska, H. Iribar, A. Izeta, P. Pytel, P. Krastel, A. Provenzani, P. Seneci, R.D. Carrasco, A. Del Sol, M.L. Martinez-Chantar, R. Barrio, E. Serra, C. Lazaro, A.M. Flanagan, M. Gorospe, N. Ratner, A.M. Aransay, A. Carracedo, M. Varela-Rey, A. Woodhoo |
| بيانات النشر: | American Society for Clinical Investigation |
| سنة النشر: | 2020 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Cancer, Cell Biology, Epigenetic, Oncogene, Oncology, Settore MED/06 - Oncologia Medica, Settore BIO/14 - Farmacologia, Settore CHIM/06 - Chimica Organica |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/32315290; info:eu-repo/semantics/altIdentifier/wos/WOS:000579392400005; volume:130; issue:7; firstpage:3848; lastpage:3864; numberofpages:17; journal:THE JOURNAL OF CLINICAL INVESTIGATION; http://hdl.handle.net/2434/754615Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85087469818 |
| DOI: | 10.1172/JCI130379 |
| الإتاحة: | https://doi.org/10.1172/JCI130379Test http://hdl.handle.net/2434/754615Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.22C9349F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1172/JCI130379 |
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