Summary of Study ST002999
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002999 |
| Study Title | 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. |
| Study 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. In this metabolomics experiment we characterize the changes in metabolic pathway flux in KP LUAD cells in response to HDAC and glutaminase inhibition. This dataset includes metabolomics of U-C13 glucose tracing (1h and 24h) and U-C13 glutamine (8h) of mouse LUAD cell lines with Kras overexpression and p53 knock-out (KP), carrying empty vector (EV) or overexpression of NRF2dNeh2 (NRF2) and treated with DMSO, Romidepsin or CB-839. 3 technical replicates were done per condition in 2 separate experiments, 1: glucose tracing and 2: glutamine tracing. |
| Institute | Columbia University - Medical Center |
| Department | Genetics and Development |
| Laboratory | Chao Lu |
| Last Name | Dimitris |
| First Name | Karagiannis |
| Address | 622 W 168th St, New York, NY 10032 |
| karagiannis_dimitrios@yahoo.gr | |
| Phone | +30 6982804931 |
| Submit Date | 2023-12-05 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-12-08 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Factors:
Subject type: Cultured cells; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype | Treatment | Timepoint | Tracer |
|---|---|---|---|---|---|
| SA326444 | EV_CB839_Gln_2 | Empty vector | CB-839 | 8 hours | U-C13 Glutamine |
| SA326445 | EV_CB839_Gln_3 | Empty vector | CB-839 | 8 hours | U-C13 Glutamine |
| SA326446 | EV_CB839_Gln_1 | Empty vector | CB-839 | 8 hours | U-C13 Glutamine |
| SA326447 | EV_DMSO_1h_3 | Empty vector | DMSO | 1 hour | U-C13 Glucose |
| SA326448 | EV_DMSO_1h_1 | Empty vector | DMSO | 1 hour | U-C13 Glucose |
| SA326449 | EV_DMSO_1h_2 | Empty vector | DMSO | 1 hour | U-C13 Glucose |
| SA326450 | EV_DMSO_24h_2 | Empty vector | DMSO | 24 hours | U-C13 Glucose |
| SA326451 | EV_DMSO_24h_1 | Empty vector | DMSO | 24 hours | U-C13 Glucose |
| SA326452 | EV_DMSO_24h_3 | Empty vector | DMSO | 24 hours | U-C13 Glucose |
| SA326453 | EV_DMSO_Gln_3 | Empty vector | DMSO | 8 hours | U-C13 Glutamine |
| SA326454 | EV_DMSO_Gln_2 | Empty vector | DMSO | 8 hours | U-C13 Glutamine |
| SA326455 | EV_DMSO_Gln_1 | Empty vector | DMSO | 8 hours | U-C13 Glutamine |
| SA326456 | EV_Rom_1h_2 | Empty vector | Romidepsin | 1 hour | U-C13 Glucose |
| SA326457 | EV_Rom_1h_1 | Empty vector | Romidepsin | 1 hour | U-C13 Glucose |
| SA326458 | EV_Rom_1h_3 | Empty vector | Romidepsin | 1 hour | U-C13 Glucose |
| SA326459 | EV_Rom_24h_2 | Empty vector | Romidepsin | 24 hours | U-C13 Glucose |
| SA326460 | EV_Rom_24h_3 | Empty vector | Romidepsin | 24 hours | U-C13 Glucose |
| SA326461 | EV_Rom_24h_1 | Empty vector | Romidepsin | 24 hours | U-C13 Glucose |
| SA326462 | EV_ROM_Gln_2 | Empty vector | Romidepsin | 8 hours | U-C13 Glutamine |
| SA326463 | EV_ROM_Gln_1 | Empty vector | Romidepsin | 8 hours | U-C13 Glutamine |
| SA326464 | EV_ROM_Gln_3 | Empty vector | Romidepsin | 8 hours | U-C13 Glutamine |
| SA326465 | QC2 | NA | NA | NA | NA |
| SA326466 | QC3 | NA | NA | NA | NA |
| SA326467 | QC4 | NA | NA | NA | NA |
| SA326468 | QC1 | NA | NA | NA | NA |
| SA326469 | QC_4 | NA | NA | NA | NA |
| SA326470 | QC_2 | NA | NA | NA | NA |
| SA326471 | QC5 | NA | NA | NA | NA |
| SA326472 | QC_3 | NA | NA | NA | NA |
| SA326473 | blank1 | NA | NA | NA | NA |
| SA326474 | blank4 | NA | NA | NA | NA |
| SA326475 | Blank_1 | NA | NA | NA | NA |
| SA326476 | QC_1 | NA | NA | NA | NA |
| SA326477 | blank2 | NA | NA | NA | NA |
| SA326478 | blank3 | NA | NA | NA | NA |
| SA326479 | NRF2_CB839_Gln_3 | NRF2 overexpression | CB-839 | 8 hours | U-C13 Glutamine |
| SA326480 | NRF2_CB839_Gln_2 | NRF2 overexpression | CB-839 | 8 hours | U-C13 Glutamine |
| SA326481 | NRF2_CB839_Gln_1 | NRF2 overexpression | CB-839 | 8 hours | U-C13 Glutamine |
| SA326482 | NRF2_DMSO_1h_1 | NRF2 overexpression | DMSO | 1 hour | U-C13 Glucose |
| SA326483 | NRF2_DMSO_1h_3 | NRF2 overexpression | DMSO | 1 hour | U-C13 Glucose |
| SA326484 | NRF2_DMSO_1h_2 | NRF2 overexpression | DMSO | 1 hour | U-C13 Glucose |
| SA326485 | NRF2_DMSO_24h_3 | NRF2 overexpression | DMSO | 24 hours | U-C13 Glucose |
| SA326486 | NRF2_DMSO_24h_2 | NRF2 overexpression | DMSO | 24 hours | U-C13 Glucose |
| SA326487 | NRF2_DMSO_24h_1 | NRF2 overexpression | DMSO | 24 hours | U-C13 Glucose |
| SA326488 | NRF2_DMSO_Gln_2 | NRF2 overexpression | DMSO | 8 hours | U-C13 Glutamine |
| SA326489 | NRF2_DMSO_Gln_1 | NRF2 overexpression | DMSO | 8 hours | U-C13 Glutamine |
| SA326490 | NRF2_DMSO_Gln_3 | NRF2 overexpression | DMSO | 8 hours | U-C13 Glutamine |
| SA326491 | NRF2_Rom_1h_1 | NRF2 overexpression | Romidepsin | 1 hour | U-C13 Glucose |
| SA326492 | NRF2_Rom_1h_2 | NRF2 overexpression | Romidepsin | 1 hour | U-C13 Glucose |
| SA326493 | NRF2_Rom_1h_3 | NRF2 overexpression | Romidepsin | 1 hour | U-C13 Glucose |
| SA326494 | NRF2_Rom_24h_2 | NRF2 overexpression | Romidepsin | 24 hours | U-C13 Glucose |
| SA326495 | NRF2_Rom_24h_1 | NRF2 overexpression | Romidepsin | 24 hours | U-C13 Glucose |
| SA326496 | NRF2_Rom_24h_3 | NRF2 overexpression | Romidepsin | 24 hours | U-C13 Glucose |
| SA326497 | NRF2_ROM_Gln_3 | NRF2 overexpression | Romidepsin | 8 hours | U-C13 Glutamine |
| SA326498 | NRF2_ROM_Gln_2 | NRF2 overexpression | Romidepsin | 8 hours | U-C13 Glutamine |
| SA326499 | NRF2_ROM_Gln_1 | NRF2 overexpression | Romidepsin | 8 hours | U-C13 Glutamine |
| Showing results 1 to 56 of 56 |
