High MITF Expression Is Associated with Super-Enhancers and Suppressed by CDK7 Inhibition in Melanoma.

ABSTRACT: Cutaneous melanoma is an aggressive tumor that accounts for most skin cancer deaths. Among the physiological barriers against therapeutic success is a strong survival program driven by genes such as MITF that specify melanocyte identity, a phenomenon known in melanoma biology as lineage dependency. MITF overexpression is occasionally explained by gene amplification, but here we show that super-enhancers are also important determinants of MITF overexpression in some melanoma cell lines and tumors. Although compounds that directly inhibit MITF are unavailable, a covalent CDK7 inhibitor, THZ1, has recently been shown to potently suppress the growth of various cancers through the depletion of master transcription-regulating oncogenes and the disruption of their attendant super-enhancers. We al

SUBMITTER: Eliades P 

PROVIDER: S-EPMC6019629 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature