Project description:The UTX/KDM6A gene encodes the UTX histone H3K27 demethylase, which plays an important role in mammalian development and is frequently mutated in cancers and particularly, in urothelial cancers. Using BioID technique, we explored the interactome of different UTX isoforms.
Project description:Large-scale genome sequencing efforts of human tumors identified epigenetic modifiers as one of the most frequently mutated gene class in human cancer. However, how these mutations drive tumor development and progression is largely unknown. Here, we identify the histone demethylase KDM6A as an important tumor suppressor in solid cancers, such as liver cancer and pancreatic cancer. KDM6A-deficient tumors show hyperactivation of mTORC1 signaling, whereas endogenous KDM6A re-expression in established KDM6A-deficient tumors diminishes mTORC1 activity by fostering the expression of crucial negative pathway regulators, such as DEPTOR, TSC1, and TSC2, resulting in tumor regression. Importantly, KDM6A expression in human tumors correlates with mTORC1 activity and KDM6A-deficient tumors exhibit increased sensitivity to mTORC1 inhibition. Hence, our results link KDM6A-dependent epigenetic remodeling to mTORC1 signaling and provide a potential therapeutic strategy for KDM6A-deficient tumors.
Project description:In this study, we used conditional knockout and gene expression approaches to understand global molecular and transciptional changes due to ablation of each integrin subunit. Affymetrix MoGene-2_0-st-v1 gene chip
