New role of ID3 in melanoma adaptive drug-resistance

作者：Sachindra; Larribere, Lionel; Novak, Daniel; Wu, Huizi; Hueser, Laura; Granados, Karol; Orouji, Elias; Utikal, Jochen^*

来源：Oncotarget, 2017, 8(66): 110166-110175.

DOI：10.18632/oncotarget.22698

• melanoma
• ID3
• drug-resistance
• targeted therapy
• BRAF

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 TGF beta/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.

• 出版日期2017-12-15
• 单位中南大学