Combined BET and MEK Inhibition synergistically suppresses melanoma by targeting YAP1
Rui Hu, Hou H, Yao Li, Minghui Zhang, Xin Li, Yanzhong Chen, Ying Guo, Hongyin Sun, Shuang Zhao, Mengting Liao, Dongsheng Cao, Qin Yan, Xiang Chen, Mingzhu Yin
Abstract
We identified a new vulnerability for MEK inhibitor-resistant melanomas, which activated Hippo pathway due to elevated YAP1 activity. Inhibition of BRD4 using BET inhibitors suppressed YAP1 expression and led to blunted melanoma growth when combined with treatment with the MEK inhibitor trametinib.
Topics & Concepts
YAP1TrametinibMEK inhibitorMelanomaCancer researchHippo signaling pathwayDownregulation and upregulationBiologyChemistryMAPK/ERK pathwaySignal transductionCell biologyTranscription factorGeneBiochemistryProtein Degradation and InhibitorsHippo pathway signaling and YAP/TAZUbiquitin and proteasome pathways