Increased CD271 expression by the NF-kB pathway promotes melanoma cell survival and drives acquired resistance to BRAF inhibitor vemurafenib
| العنوان: | Increased CD271 expression by the NF-kB pathway promotes melanoma cell survival and drives acquired resistance to BRAF inhibitor vemurafenib |
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| المؤلفون: | Lehraiki, Abdelali, Cerezo, Michaël, Rouaud, Florian, Abbe, Patricia, Allegra, Marilyne, Kluza, Jerome, Marchetti, Philippe, Imbert, Véronique, Cheli, Yann, Bertolotto, Corine, Ballotti, Robert, Rocchi, Stéphane |
| المساهمون: | Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 (JPArc), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Université de Lille, This research was supported by the INSERM, University of Nice Sophia Antipolis, ARC contract n° PJA 20141201849, SILAB fondation and the ‘INCA Recherche Translationnelle 2011’. AL is a recipient of a doctoral fellowship from the ‘Fondation de France’. INSERM U1065, team 1 is ‘équipe labelisée ligue 2013’., Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 (JPArc), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI |
| المصدر: | Cell Discovery Cell Discovery, 2015, 1, pp.15030. ⟨10.1038/celldisc.2015.30⟩ |
| بيانات النشر: | HAL CCSD, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | resistance, [SDV.CAN] Life Sciences [q-bio]/Cancer, TNFα, melanoma, vemurafenib, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, NF-κB, CD271 |
| الوصف: | International audience; Specific BRAFV600E inhibitors (BRAFi) are highly effective in the treatment of melanoma. However, acquired drug resistances invariably develop after the initial response. Therefore, the identification of new mechanisms of acquired resistance gives important clues towards the development of therapies that could elicit long lasting responses. Here we report that CD271 confers resistance to BRAFi in melanoma cells. The expression of CD271 is increased by BRAFi through a stimulation of tumor necrosis factor-alpha (TNFα) secretion that leads to NF-κB signaling pathway activation. CD271 is upregulated in a subset of BRAFi-resistant melanoma cells. The inhibition of TNFα/NF-κB pathway and CD271 silencing restore the BRAFi sensitivity of resistant melanoma cells. Finally, increase of CD271 expression is validated in BRAFi-resistant xenografts tumors and also in tumors from the patients who relapsed under BRAFi. In summary, these results reveal a novel TNFα/NF-κB/CD271 axis whose activation contributes to the acquisition of resistance to BRAFi and therefore may represent a novel therapeutic target to improve the efficacy of therapy in melanoma. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::dc095f11230dff506671fcd2bf64eb97 https://www.hal.inserm.fr/inserm-02530554 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.pmid.dedup....dc095f11230dff506671fcd2bf64eb97 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |