Summary of project PR001869
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001869. The data can be accessed directly via it's Project DOI: 10.21228/M84F0M This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001869 |
| Project DOI: | doi: 10.21228/M84F0M |
| Project Title: | Metabolic Reprogramming by Histone Deacetylase Inhibition Preferentially Targets NRF2-activated tumors |
| Project Summary: | Interplay between metabolism and chromatin signaling are implicated in cancer progression. However, whether and how metabolic reprogramming in tumors generates chromatin vulnerabilities remain unclear. Lung adenocarcinoma (LUAD) tumors frequently harbor aberrant activation of the NRF2 antioxidant pathway which drives aggressive and chemo-resistant disease. Using a chromatin-focused CRISPR screen we report that NRF2 activation sensitizes LUAD cells to genetic and chemical inhibition of class I histone deacetylases (HDAC). This association is observed across cultured cells, mouse models and patient-derived xenografts. Integrative epigenomic, transcriptomic and metabolomic analysis demonstrates that HDAC inhibition causes widespread redistribution of H4ac and its reader protein, which transcriptionally downregulates metabolic enzymes. This results in reduced flux into amino acid metabolism and de novo nucleotide synthesis pathways that are preferentially required for the survival of NRF2-active cancer cells. Together, our findings suggest NRF2 activation as a potential biomarker for effective repurposing of HDAC inhibitors to treat solid tumors. |
| Institute: | Columbia University Medical Center |
| Department: | Genetics and Development |
| Laboratory: | Chao Lu |
| Last Name: | Karagiannis |
| First Name: | Dimitris |
| Address: | 630 West 168th Street, NEW YORK, NY, 10032, USA |
| Email: | karagiannis_dimitrios@yahoo.gr |
| Phone: | +30 6982804931 |
Summary of all studies in project PR001869
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002999 | Metabolomics and glucose and glutamine labeled isotope tracing analysis in murine lung adenocarcinoma cells in the context of normal or active NRF2 pathway as well as HDAC and glutaminase inhibitor treatment. | Mus musculus | Columbia University - Medical Center | MS | 2023-12-08 | 1 | 56 | Uploaded data (1.2G)* |
