Summary of project PR001659
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 PR001659. The data can be accessed directly via it's Project DOI: 10.21228/M8872J This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001659 |
| Project DOI: | doi: 10.21228/M8872J |
| Project Title: | AKT activation due to PTEN loss upregulates xCT via the GSK3beta/NRF2 axis resulting in inhibition of ferroptosis and revealing a novel tumor suppressive property of PTEN |
| Project Type: | Quantitative Targeted Mass Spec |
| Project Summary: | Here we show that the tumor suppressor PTEN sensitizes cells to ferroptosis, an iron dependent form of cell death, by restraining the expression and activity of the cystine/glutamate antiporter, system Xc- (xCT), and augmenting cysteine metabolism. Loss of PTEN activated AKT kinase to inhibit GSK3beta, increasing NRF2 along with transcription of one of its known target genes encoding xCT. Elevated xCT in Pten-null mouse embryonic fibroblasts increased the flux of cystine transport and the synthesis of glutathione, which enhanced the steady state levels of these metabolites. A pan cancer analysis revealed that loss of PTEN shows evidence of increased xCT and PTEN mutant cells were found to be resistant to ferroptosis as a consequence of elevated xCT. These findings suggest that selection of PTEN mutation during tumor development may be due to its ability to confer resistance to ferroptosis in the setting of metabolic stress that occurs during tumor initiation and progression. |
| Institute: | Mount Sinai Oncological Sciences Department |
| Laboratory: | Ramon Parsons Laboratory |
| Last Name: | Cahuzac |
| First Name: | Kaitlyn |
| Address: | 6358 Lucent Lane, Atlanta, GA, 30328, USA |
| Email: | kaitlyncahuzac@gmail.com |
| Phone: | 6784537911 |
Summary of all studies in project PR001659
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002572 | Steady State and Cysteine Flux Metabolomics Study in PTEN WT and PTEN KO MEFs | Mus musculus | Mount Sinai | MS | 2023-04-23 | 1 | 6 | Not available |
| ST002573 | Steady State and Cystine Flux Metabolomics Study in PTEN WT and PTEN KO MEFs | Mus musculus | Mount Sinai | MS | 2023-04-23 | 1 | 10 | Not available |
