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.
| Study ID | ST003051 |
| Study Title | Shotgun lipidomics of breast cancer endocrine therapy persisters |
| Study Type | Lipidomics |
| Study Summary | Despite 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 |
| Department | Molecular and Systems Biology |
| Laboratory | Todd Miller Lab |
| Last Name | Miller |
| First Name | Todd |
| Address | Hanover, NH |
| Todd.W.Miller@Dartmouth.edu | |
| Phone | 603-646-5507 |
| Submit Date | 2024-01-17 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | wiff |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-02-13 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001900 |
| Project DOI: | doi: 10.21228/M84729 |
| Project Title: | Oxidative stress of breast cancer endocrine therapy persisters |
| Project Type: | MS |
| Project Summary: | Investigation of the oxidative state of persisters tolerant to endocrine therapy of breast cancer, with a focus on mechanism and therapeutic targeting |
| Institute: | University of Michigan |
| Department: | MRC2 |
| Last Name: | Kachman |
| First Name: | Maureen |
| Address: | Ann Arbor, MI, USA |
| Email: | mkachman@med.umich.edu |
| Phone: | 734-232-0842 |
Subject:
| Subject ID: | SU003166 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Hormone treatment |
|---|---|---|
| SA331404 | Plasma pool | No |
| SA331405 | T47D fulv_3 | No |
| SA331406 | T47D fulv_2 | No |
| SA331407 | T47D fulv_1 | No |
| SA331411 | Test pool | pooled |
| SA331408 | T47D veh_3 | Yes |
| SA331409 | T47D veh_1 | Yes |
| SA331410 | T47D veh_2 | Yes |
| Showing results 1 to 8 of 8 |
Collection:
| Collection ID: | CO003159 |
| Collection Summary: | Cells were washed with 150 mM ammonium acetate and flash frozen, before storage at -80deg C. |
| Sample Type: | Breast cancer cells |
Treatment:
| Treatment ID: | TR003175 |
| Treatment Summary: | The ER+ breast cancer cell line was subject to 1 uM of the selective estrogen receptor degrader (SERD), fulvestrant, with vehicle control control. Cells were subjected to treatment for 7 days, before reseeding into 10 cm dishes at 3-5e6 cells/dish. |
Sample Preparation:
| Sampleprep ID: | SP003172 |
| Sampleprep Summary: | Standard lipidomics protocol. See protocol file. |
| Sampleprep Protocol Filename: | A004_Shotgun_Lipidomics.PDF |
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 |
MS:
| MS ID: | MS004742 |
| Analysis ID: | AN005002 |
| Instrument Name: | ABI Sciex 5600+ TripleTOF |
| Instrument Type: | Triple TOF |
| MS Type: | ESI |
| MS Comments: | Acquisition of MS/MS spectra was controlled by data dependent acquisition (DDA) function of the Analyst TF software. Lipids are identified using LIPIDBLAST package. Quantification of lipids is done by Multiquant software (AB-SCIEX). Normalization of the data for different lipid classes is performed based on a set of internal standards. |
| Ion Mode: | POSITIVE |
| Acquisition Parameters File: | LIP_15min_MSMS_Jenny_new_20min_mass100-1200_Valve_Positive.txt |
| MS ID: | MS004743 |
| Analysis ID: | AN005003 |
| Instrument Name: | ABI Sciex 5600+ TripleTOF |
| Instrument Type: | Triple TOF |
| MS Type: | ESI |
| MS Comments: | Acquisition of MS/MS spectra was controlled by data dependent acquisition (DDA) function of the Analyst TF software. Lipids are identified using LIPIDBLAST package. Quantification of lipids is done by Multiquant software (AB-SCIEX). Normalization of the data for different lipid classes is performed based on a set of internal standards. |
| Ion Mode: | NEGATIVE |
| Acquisition Parameters File: | LIP_15min_MSMS_Jenny_New_20min_valve_Negative.txt |
