New role of ID3 in melanoma adaptive drug-resistance
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Sachindra1,2,*, Lionel Larribère1,2,*, Daniel Novak1,2, Huizi Wu1,2,3, Laura Hüser1,2, Karol Granados1,2, Elias Orouji1,2,4 and Jochen Utikal1,2
1Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany
2Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls University of Heidelberg, Mannheim, Germany
3Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China
4Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
*These authors contributed equally to this work
Jochen Utikal, email: firstname.lastname@example.org
Lionel Larribère, email: email@example.com
Keywords: melanoma; ID3; drug-resistance; targeted therapy; BRAF
Received: May 11, 2017 Accepted: October 27, 2017 Published: November 27, 2017
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.
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