KMT2D deficiency confers a therapeutic vulnerability to glycolytic and IGFR inhibitors in melanoma

Mol Cell Oncol. 2021 Nov 1;8(5):1984827. doi: 10.1080/23723556.2021.1984827. eCollection 2021.

Abstract

We reported that histone H3 lysine (K) 4 methyltransferase, KMT2D, serves as a potent tumor-suppressor in melanoma, which was identified via in vivo epigenome-focused RNA interference (RNAi) screen. KMT2D-deficient tumors show substantial reprogramming of key metabolic pathways including glycolysis via reduction of H3K4me1 (Histone H3K4 mono-methylation)-marked active enhancers, conferring sensitivity to inhibitors of glycolysis and IGFR (Insulin Growth Factor Receptor) pathway.

Keywords: KMT2D; enhancer reprogramming; glycolysis; melanoma.