Summary of project PR002015
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 PR002015. The data can be accessed directly via it's Project DOI: 10.21228/M85238 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002015 |
| Project DOI: | doi: 10.21228/M85238 |
| Project Title: | Zeb1-mediated control of the phospholipid PUFA/MUFA ratio in EMT/plasticity-associated 1 cancer cell ferroptosis |
| Project Summary: | Therapy resistance and metastasis, the most fatal steps in cancer, are often triggered by a (partial) activation of the epithelial-mesenchymal-transition (EMT)-program. A mesenchymal phenotype predisposes to ferroptosis, a cell death pathway exerted by an iron and oxygen-radical mediated peroxidation of phospholipids containing polyunsaturated fatty acids (PUFAs). We here describe that various forms of EMT-activation increase ferroptosis-susceptibility in cancer cells, which depends on the EMT-transcription factor Zeb1. To further investigate the underlying mechanisms of an EMT/Zeb1-coupled ferroptosis sensitivity, we analyzed key determinants of ferroptotic cell death, focusing on the proportion and (per)oxidation of fatty acid species in phospholipid subclasses. Using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we demonstrate that GPX4 inhibition in human breast cancer MDA-MB-231 cells (Zeb1high) led to a rapid (per)oxidation of PUFA-containing phospholipids (oxPL), which is absent in cells depleted of Zeb1 (shZeb1). Mechanistically, Zeb1 increases the ratio of phospholipids containing pro-ferroptotic PUFAs over cyto-protective monounsaturated fatty acids (MUFAs) in MDA-MB-231 cells, tumor-derived pancreatic cancer KPC cells as well as mice tumor allografts via the modulation of crucial lipogenic enzymes. |
| Institute: | University of Innsbruck |
| Department: | Michael Popp Institute |
| Last Name: | Koeberle |
| First Name: | Andreas |
| Address: | Mitterweg 24, Innsbruck, Tyrol, 6020, Austria |
| Email: | Andreas.Koeberle@uibk.ac.at |
| Phone: | +43 512 507 57903 |
| Funding Source: | the Austrian Science Fund (FWF) (P 36299), the German Research Council (GRK 1715), and the Phospholipid Research Center (Grant Number AKO‐2019‐070/2‐1, AKO-2O22-100/2-2), the Tyrolean Science Fund (TWF) (F.33467/7-2021). |
| Publications: | in revision |
| Contributors: | Zhigang Rao, Jie Zhang, André Gollowitzer, Leonhard Bereuter, Andreas Koeberle |
Summary of all studies in project PR002015
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003245 | Exploration of Zeb1-dependent changes in the lipidome of MDA-MB-231 cells | Homo sapiens | University of Innsbruck | MS | 2024-07-05 | 1 | 48 | Uploaded data (8.2M)* |
| ST003256 | Exploration of Zeb1-dependent changes in the redox-lipidome of MDA-MB-231 cells | Homo sapiens | University of Innsbruck | MS | 2024-07-05 | 1 | 69 | Uploaded data (5.6M)* |
| ST003257 | Exploration of EMT-dependent changes in the lipidome of KPC cells | Mus musculus | University of Innsbruck | MS | 2024-07-05 | 1 | 27 | Uploaded data (3.5M)* |
| ST003259 | Exploration of EMT-dependent changes of phosphatidylethanolamine profiles in KPC allografts | Mus musculus | University of Innsbruck | MS | 2024-07-05 | 1 | 6 | Uploaded data (1.1M)* |
