Summary of Study ST003245
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003245 |
| Study Title | Exploration of Zeb1-dependent changes in the lipidome of MDA-MB-231 cells |
| Study Summary | Human breast cancer MDA-MB-231 wildtype (WT) cells and the stably transduced MDA-MB-231 shZeb1 (stable Zeb1 knockdown) and shCtrl cell lines (control cell line for the stable Zeb1 knockdown) (Spaderna et al. 2008, DOI: 10.1158/0008-5472.CAN-07-5682) were analyzed for their phospholipid profile by UPLC-MS/MS. Please note that one sample set was measured three times with the same sample-ID, but with different methods (PE, PC, PI), therefore each sub-class has their own raw-data file marked by their corresponding abbreviation (PE, PC, PI; e.g. "210514_MDA_ZEB1_PE_dil_1_10_std_1ul_JZ_PE_MRM_002.wiff", "210514_MDA_ZEB1_PC_dil_1_10_std_1ul_JZ_PC_MRM_002.wiff" or "210514_MDA_ZEB1_PC_dil_1_10_std_1ul_JZ_PC_MRM_002.wiff"). |
| Institute | University of Innsbruck |
| Department | Michael Popp Institute |
| Last Name | Koeberle |
| First Name | Andreas |
| Address | Mitterweg 24, Innsbruck, Tyrol, 6020, Austria |
| Andreas.Koeberle@uibk.ac.at | |
| Phone | +43 512 507 57903 |
| Submit Date | 2024-05-27 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | wiff |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-07-05 |
| Release Version | 1 |
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Project:
| 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 |
