2026-04-30T20:32:17Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/252152025-04-04T09:04:56Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16962
Repisalud author Hernandez-Muñoz, Inmaculada author Figuerola, Elisabeth author Sanchez-Molina, Sara author Rodriguez, Eva author Fernández-Mariño, Ana Isabel author Pardo-Pastor, Carlos author Bahamonde, María Isabel author Fernández-Fernández, José M author García-Domínguez, Daniel J author Hontecillas-Prieto, Lourdes author Lavarino, Cinzia author Carcaboso, Angel M author de Torres, Carmen author Tirado, Oscar M author de Álava, Enrique author Mora, Jaume 2024-10-23T09:08:09Z 2024-10-23T09:08:09Z 2016 10.18632/oncotarget.10092 1949-2553 Oncotarget http://hdl.handle.net/10668/19432 27317769 https://hdl.handle.net/20.500.12105/25215 Ewing sarcoma (ES) is an aggressive tumor defined by EWSR1 gene fusions that behave as an oncogene. Here we demonstrate that RING1B is highly expressed in primary ES tumors, and its expression is independent of the fusion oncogene. RING1B-depleted ES cells display an expression profile enriched in genes functionally involved in hematological development but RING1B depletion does not induce cellular differentiation. In ES cells, RING1B directly binds the SCN8A sodium channel promoter and its depletion results in enhanced Nav1.6 expression and function. The signaling pathway most significantly modulated by RING1B is NF-κB. RING1B depletion results in enhanced p105/p50 expression, which sensitizes ES cells to apoptosis by FGFR/SHP2/STAT3 blockade. Reduced NaV1.6 function protects ES cells from apoptotic cell death by maintaining low NF-κB levels. Our findings identify RING1B as a trait of the cell-of-origin and provide a potential targetable vulnerability. eng Ewing sarcoma FGFR/SHP2/STAT3 NF-κB RING1B voltage-gated sodium channel RING1B contributes to Ewing sarcoma development by repressing the NaV1.6 sodium channel and the NF-κB pathway, independently of the fusion oncoprotein research article