Summary of Study ST003051

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 PR001900. The data can be accessed directly via it's Project DOI: 10.21228/M84729 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.

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Study IDST003051
Study TitleShotgun lipidomics of breast cancer endocrine therapy persisters
Study TypeLipidomics
Study SummaryDespite adjuvant endocrine therapy, the rate of ER+ breast cancer recurrence remains high. The metabolic state of cells that remain after endocrine therapy, specifically oxidative stress, is poorly understood. We demonstrate that endocrine-tolerant persister cells are oxidatively stressed after initiation of endocrine therapy. Furthermore, modulation of redox levels similarly modifies persister cell fitness. We find ferroptosis sensitivity and lipid peroxidation to be a dominant factor in the oxidative state, and persister cells are found to be sensitive to ferroptosis induction compared to parental cells. Persister cells exhibited an altered lipidome, with an increase in phospholipids having a predilection for peroxidation. We hypothesized that ferroptosis induction would be well-coordinated with endocrine therapy. Xenografts treated with a combination of fulvestrant and ferroptosis induction exhibited the greatest treatment effect, supporting the role of ferroptosis as a therapeutic strategy in ER+ breast cancer.
Institute
Dartmouth College
DepartmentMolecular and Systems Biology
LaboratoryTodd Miller Lab
Last NameMiller
First NameTodd
AddressHanover, NH
EmailTodd.W.Miller@Dartmouth.edu
Phone603-646-5507
Submit Date2024-01-17
Raw Data AvailableYes
Raw Data File Type(s)wiff
Analysis Type DetailLC-MS
Release Date2024-02-13
Release Version1
Todd Miller Todd Miller
https://dx.doi.org/10.21228/M84729
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN005002 AN005003
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Shimadzu LC-30 Shimadzu LC-30
Column Waters ACQUITY UPLC HSS T3 (50 x 2.1mm,1.8um) Waters ACQUITY UPLC HSS T3 (50 x 2.1mm,1.8um)
MS Type ESI ESI
MS instrument type Triple TOF Triple TOF
MS instrument name ABI Sciex 5600+ TripleTOF ABI Sciex 5600+ TripleTOF
Ion Mode POSITIVE NEGATIVE
Units counts counts

Chromatography:

Chromatography ID:CH003780
Chromatography Summary:Positive mode lipidomics LC-MSMS
Instrument Name:Shimadzu LC-30
Column Name:Waters ACQUITY UPLC HSS T3 (50 x 2.1mm,1.8um)
Column Temperature:55
Flow Gradient:(Time : Pump B%) (0.01 : 40) (10.00 : 98) (17.00 : 98) (17.10 : 40)
Flow Rate:0.4 ml/min
Solvent A:Acetonitrile / water (40:60, v/v) with 10 mM ammonium acetate
Solvent B:Acetonitrile / water / isopropanol (10 : 5 : 85 v/v) with 10 mM ammonium acetate
Chromatography Type:Reversed phase
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