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New role of ID3 in melanoma adaptive drug-resistance

2017; Impact Journals LLC; Volume: 8; Issue: 66 Linguagem: Inglês

10.18632/oncotarget.22698

1949-2553

Sachindra, Lionel Larribère, Daniel Novak, Huizi Wu, Laura Hüser, Karol Granados, Elias Orouji, Jochen Utikal,

Cytokine Signaling Pathways and Interactions

// Sachindra 1, 2, * , Lionel Larribère 1, 2, * , Daniel Novak 1, 2 , Huizi Wu 1, 2, 3 , Laura Hüser 1, 2 , Karol Granados 1, 2 , Elias Orouji 1, 2, 4 and Jochen Utikal 1, 2 1 Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany 2 Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany 3 Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China 4 Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA * These authors contributed equally to this work Correspondence to: Jochen Utikal, email: j.utikal@dkfz.de Lionel Larribère, email: l.larribere@dkfz.de Keywords: melanoma; ID3; drug-resistance; targeted therapy; BRAF Received: May 11, 2017 Accepted: October 27, 2017 Published: November 27, 2017 ABSTRACT Adaptive resistance to targeted therapy such as BRAF inhibitors represents in melanoma a major drawback to this otherwise powerful treatment. Some of the underlying molecular mechanisms have recently been described: hyperactivation of the BRAF-MAPK pathway, of the AKT pathway, of the TGFβ/EGFR/PDGFRB pathway, or the low MITF/AXL ratio. Nevertheless, the phenomenon of early resistance is still not clearly understood. In this report, we show that knockdown of neural crest-associated gene ID3 increases the melanoma sensitivity to vemurafenib short-term treatment. In addition, we observe an ID3 -mediated regulation of cell migration and of the expression of resistance-associated genes such as SOX10 and MITF . In sum, these data suggest ID3 as a new key actor of melanoma adaptive resistance to vemurafenib and as a potential drug target.