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KDM6A(UTX) is an epigenetic gatekeeper of mTORC1 signalling in cancer

UID: 11021

Author(s): Revia, Steffie, Tschaharganeh, Darjus F.* * MSK affiliated

Description
Summary from GEO:

"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."

Overall design from GEO:

"Examination of 2 different genotypes of primary liver cancer cell lines, Myc_Utx (derived from murine KDM6A-deficient tumor) and Myc_p53 (as control, derived from murine p53 knockout tumor). Three biological replicates (tumor from different mice) were used in this study for each genotype. For Myc_Utx: Myc_Utx_2A, Myc_Utx_2B and Myc_Utx_2D cell lines were used. As reference/control, Myc_p53: Myc_p53_1, Myc_p53_2 and Myc_p53_3 were used."
Subject of Study
Subject(s)
Access via GEO


Accession #: GSE155630

Access via BioProject


Accession #: PRJNA650533

Access via SRA


Accession #: SRP275686

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus. BioProject, and SRA databases provide open access to these files.
Associated Publications
Equipment Used
Illumina HiSeq 2500
Dataset Format(s)
CSV
Dataset Size
4.2 MB
Data Catalog Record Updated
2023-11-09