Summary of project PR002015

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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.


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
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 IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : 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)*