Summary of project PR001843
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 PR001843. The data can be accessed directly via it's Project DOI: 10.21228/M8GT6S This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001843 |
| Project DOI: | doi: 10.21228/M8GT6S |
| Project Title: | G6PD Maintains Redox Homeostasis and Biosynthesis in LKB1-Deficient KRAS-Driven Lung Cancer |
| Project Summary: | Cancer cells depend on nicotinamide adenine dinucleotide phosphate (NADPH) to combat oxidative stress and support reductive biosynthesis. One major NAPDH production route is the oxidative pentose phosphate pathway (committed step: glucose-6-phosphate dehydrogenase, G6PD). Alternatives exist and can compensate in some tumors. Here, using genetically-engineered lung cancer model, we show that ablation of G6PD significantly suppresses KrasG12D/+;Lkb1-/- (KL) but not KrasG12D/+;p53-/- (KP) lung tumorigenesis. In vivo isotope tracing and metabolomics revealed that G6PD ablation significantly impaired NADPH generation, redox balance and de novo lipogenesis in KL but not KP lung tumors. Mechanistically, in KL tumors, G6PD ablation caused p53 activation that suppressed tumor growth. As tumor progressed, G6PD-deficient KL tumors increased an alternative NADPH source, serine-driven one carbon metabolism, rendering associated tumor-derived cell lines sensitive to serine/glycine depletion. Thus, oncogenic driver mutations determine lung cancer dependence on G6PD, whose targeting is a potential therapeutic strategy for tumors harboring KRAS and LKB1 co-mutations. |
| Institute: | Rutgers Cancer Institute of New Jersey |
| Last Name: | Guo |
| First Name: | Jessie Yanxiang |
| Address: | Room 3028, 195 Little Albany Street |
| Email: | yanxiang@cinj.rutgers.edu |
| Phone: | 17327632262 |
| Funding Source: | R01CA237347-01A1, ACS 134036-RSG-19-165-01-TBG, GO2 Foundation for Lung Cancer, and Ludwig Princeton Branch of the Ludwig Institute for Cancer Research to J.Y.G. R01CA163591 and Ludwig Princeton Branch of the Ludwig Institute for Cancer Research to E.W. NIH P30 CA072720 to Rutgers Cancer Institute of New Jersey |
Summary of all studies in project PR001843
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002962 | LC/MS detection for NADPH and NADP+ levels in KRAS-driven lung tumors with LKB1 or p53 deficiency, comparing cases with G6PD wild-type and G6PD knockout | Mus musculus | Rutgers Cancer Institute of New Jersey | MS | 2024-01-16 | 1 | 33 | Uploaded data (475.2M)* |
| ST002963 | LC/MS detection for GSH and GSSG levels in KRAS-driven lung tumors with LKB1 or p53 deficiency, comparing cases with G6PD wild-type and G6PD knockout | Mus musculus | Rutgers Cancer Institute of New Jersey | MS | 2024-01-16 | 1 | 33 | Uploaded data (1G)* |
