Summary of project PR002208
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 PR002208. The data can be accessed directly via it's Project DOI: 10.21228/M86Z6P This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002208 |
| Project DOI: | doi: 10.21228/M86Z6P |
| Project Title: | NRF2 supports non-small cell lung cancer growth independently of CBP/p300-enhanced glutathione synthesis |
| Project Type: | MS quantitative analysis |
| Project Summary: | Nuclear factor erythroid 2-related factor 2 (NRF2) is a stress responsive transcription factor that is mutationally activated in a subset (~25%) of clinically-aggressive non-small cell lung cancers (NSCLC). Mechanistic insight into drivers of the NRF2 dependency remains poorly understood. Here, we defined a novel NRF2 target gene set linked to NRF2-dependency in cancer cell lines, and observed that a significant portion of these genes is devoid of promoter-proximal NRF2. Using integrated genomic analyses, we characterized extensive NRF2-dependent enhancer RNA (eRNA) synthesis and NRF2-mediated H3K27ac deposition at proximal and distal enhancer regions regulating these genes. While CBP/p300 is a well-validated direct interaction partner of NRF2 with prominent functions at enhancers, we report that this interaction is not required for NRF2-dependent NSCLC cell growth, indicating that NRF2 can sustain sufficient transcriptional activity in the absence of CBP/p300 coactivation. Broad metabolic profiling established a primary role for CBP/p300 in NRF2-dependent accumulation of glutathione and glutathione-related metabolites. While redox homeostasis via enhanced glutathione production is commonly associated with the normal physiological role of NRF2, collectively our results suggest that NRF2-dependent cancer cell growth does not require this enhanced glutathione production. |
| Institute: | Genentech Inc. |
| Last Name: | Wong |
| First Name: | Weng Ruh |
| Address: | 1 DNA Way, South San Francisco, CA 94080, USA |
| Email: | wongw24@gene.com |
| Phone: | 4089048962 |
| Contributors: | Ryan J. Conrad, James A. Mondo, Mike Lingjue Wang, Peter S. Liu, Zijuan Lai, Feroza K Choudhury, Qingling Li, Weng Ruh Wong, James Lee, Frances Shanahan, Eva Lin, Scott Martin, Joachim Rudolph, John G. Moffat, Dewakar Sangaraju, Wendy Sandoval, Timothy Sterne-Weiler, Scott A. Foster |
Summary of all studies in project PR002208
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003578 (Available on 2025-03-31) | NRF2 supports non-small cell lung cancer growth independently of CBP/p300-enhanced glutathione synthesis | Homo sapiens | Genentech Inc. | MS | - | - | 24 | Not available |
| ST003623 | NRF2 supports non-small cell lung cancer growth independently of CBP/p300-enhanced glutathione synthesis: Global metabolomics analysis on A549 cells at different NRF2 status (Part 1 of 3) | Homo sapiens | Genentech Inc. | MS | 2025-01-02 | 1 | 32 | Uploaded data (333M)* |
| ST003624 | NRF2 supports non-small cell lung cancer growth independently of CBP/p300-enhanced glutathione synthesis: Absolute Quantification of NADP+ and NADPH in A549 cells (Part 2 of 3) | Homo sapiens | Genentech Inc. | MS | 2025-01-02 | 1 | 16 | Uploaded data (181.1M)* |
| ST003625 | NRF2 supports non-small cell lung cancer growth independently of CBP/p300-enhanced glutathione synthesis: Using 1,2-13C-glucose to measure PPP Flux in A549 cells (Part 3 of 3) | Homo sapiens | Genentech Inc. | MS | 2025-01-02 | 1 | 60 | Uploaded data (767.2M)* |
