Summary of project PR002607
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 PR002607. The data can be accessed directly via it's Project DOI: 10.21228/M8NZ6Q This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002607 |
| Project DOI: | doi: 10.21228/M8NZ6Q |
| Project Title: | FOXO1 links KRAS G12D and G12V alleles to glutamine and nitrogen metabolism in colorectal cancer |
| Project Summary: | Mutations in KRAS, particularly at codon 12, are frequent in adenocarcinomas of the colon, lungs and pancreas, driving carcinogenesis by altering cell signalling and reprogramming metabolism. However, the specific mechanisms by which different KRAS G12 alleles initiate distinctive patterns of metabolic reprogramming are unclear. Using isogenic panels of colorectal cell lines harbouring the G12A, G12C, G12D and G12V heterozygous mutations and employing transcriptomics, metabolomics, and extensive biochemical validation, we characterise distinctive features of each allele. We demonstrate that cells harbouring the common G12D and G12V oncogenic mutations significantly alter glutamine metabolism and nitrogen recycling through FOXO1-mediated regulation compared to parental lines. Moreover, with a combination of small molecule inhibitors targeting glutamine and glutamate metabolism, we also identify a common vulnerability that eliminates mutant cells selectively. These results highlight a previously unreported mutant-specific effect of KRAS alleles on metabolism and signalling that could be potentially harnessed for cancer therapy. |
| Institute: | Brunel University of London |
| Department: | Biosciences |
| Laboratory: | Laboratory of Quantitative Biology (Esposito group) |
| Last Name: | Esposito |
| First Name: | Alessandro |
| Address: | Brunel University of London, Kingston Lane, UB8 3PH, London, United Kingdom |
| Email: | alessandro.esposito@brunel.ac.uk |
| Phone: | 07954383731 |
Summary of all studies in project PR002607
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004144 | Metabolic rewiring in isogenic SW48 colorectal cancer cells with different oncogenic KRAS G12 point mutations | Homo sapiens | Brunel University of London | MS | 2025-08-25 | 1 | 294 | Uploaded data (33.1G)* |
