Summary of Study ST003678
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 PR002249. The data can be accessed directly via it's Project DOI: 10.21228/M8XC02 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 | ST003678 |
| Study Title | The effects of cystine limitation stress adaptation (CLSA) on lipidomics changes in pancreatic cancer cells |
| Study Summary | To determine the effects of CLSA on pancreatic cancer metabolism, lipids were extracted from control or CLSA MiaPaCA2 cells and untargeted metabolomics screening were performed. |
| Institute | Pennsylvania State University |
| Last Name | Yang |
| First Name | Shengyu |
| Address | 500 University Drive |
| sxy99@psu.edu | |
| Phone | 7175311721 |
| Submit Date | 2024-12-19 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML, raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-09-29 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002249 |
| Project DOI: | doi: 10.21228/M8XC02 |
| Project Title: | Adaptation to cystine limitation stress confers a targetable lipid metabolism vulnerability in pancreatic ductal adenocarcinoma (PDAC). |
| Project Summary: | Cystine/cysteine is critical for antioxidant response and sulfur metabolism in cancer cells and is one of the most depleted amino acids in the PDAC microenvironment. The effects of cystine limitation stress (CLS) on PDAC progression are poorly understood. Here we report that adaptation to CLS (CLSA) promotes PDAC cell proliferation and tumor growth through translational upregulation of the oxidative pentose phosphate pathway (OxPPP). OxPPP activates the de novo synthesis of nucleotides and fatty acids to support tumor growth. On the other hand, CLSA-mediated lipidomic reprogramming depends on triacylglycerides synthesis to mitigate lipotoxicity. Through drug screening, we identified lomitapide as an inhibitor of CLSA PDAC tumor growth and a potent sensitizer of FOLFIRINOX chemotherapy. Mechanistically, lomitapide inhibits triacylglycerides synthesis to interfere with CLSA and chemotherapy-induced lipidomic reprograming. Taken together, CLSA-mediated metabolic and lipidomics reprograming promotes PDAC tumor growth and lomitapide could be used to target the dysregulated lipid metabolism in PDAC. |
| Institute: | Pennsylvania State University |
| Last Name: | Yang |
| First Name: | Shengyu |
| Address: | 500 University Drive |
| Email: | sxy99@psu.edu |
| Phone: | 7175311721 |
Subject:
| Subject ID: | SU003810 |
| Subject Type: | Cultured cells |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Cell Strain Details: | MiaPaCa2 pancreatic cancer cells |
Factors:
Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Treatment |
|---|---|---|
| SA402219 | 101321PCSY4 | CLSA25 |
| SA402220 | 101321PCSY5 | CLSA25 |
| SA402221 | 101321PCSY6 | CLSA25 |
| SA402222 | 101321PCSY1 | Control |
| SA402223 | 101321PCSY2 | Control |
| SA402224 | 101321PCSY3 | Control |
| Showing results 1 to 6 of 6 |
Collection:
| Collection ID: | CO003803 |
| Collection Summary: | 1x107 cells were harvested using a cell scrapper. The cell pellets were resuspended in 100 μL dH2O containing proteinase inhibitors. 50 μL cell suspensions were used for lipid extraction while the remaining samples were used for protein assay. |
| Sample Type: | pancreatic cancer cells |
Treatment:
| Treatment ID: | TR003819 |
| Treatment Summary: | MiaPaCa-2 cells were cultured in DMEM medium (Dulbecco's Modified Eagle Medium) containing 25 μM cystine for 4 weeks to induce CLSA before being used for lipidomics study. |
Sample Preparation:
| Sampleprep ID: | SP003817 |
| Sampleprep Summary: | 10 million cells were harvested with a cell scrapper. After centrifugation the cell pellet was extracted with 1.5 mL HPLC grade methanol and vortex for 1 min. 5 mL of MTBE was added and rocked for 1 h at room temperature (RT). After addition of 1.2 mL of water and vortex again for 1 min, the mixture was centrifuged for 10 min at 1,000 g (microcentrifuge, RT). The upper MTBE liquid phase containing the non-polar lipids were collected. Re-extract the lower liquid phase with 2 volume parts of MTBE/methanol/water (10/3/2.5, v/v/v). Dry the combined MTBE phases in a SpeedVac or under a nitrogen stream. |
Chromatography:
| Chromatography ID: | CH004589 |
| Instrument Name: | Agilent 1100 |
| Column Name: | Cadenza CD-C18 HPLC column (3.0 μm) 2.0 mm i.d. x 150 mm length (Imtakt, CD025) |
| Column Temperature: | 25℃ |
| Flow Gradient: | 32% (v/v) B 0.0 min 32% B 1.5 min 45% B 4.0 min 52% B 5.0 min 58% B 8.0 min 66% B 11.0 min 70% B 14.0 min 75% B 18.0 min 97% B 21.0 min 97% B 25.0 min 32% B 26.0 min 32% B 32.0 min |
| Flow Rate: | ~200–270 μL/min |
| Solvent A: | 60% Acetonitrile/40% Water; 10mM ammonium formate; 0.1% formic acid |
| Solvent B: | 90% Isopropanol/10% Acetonitrile; 10mM ammonium formate; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN006039 |
| Analysis Type: | MS |
| Chromatography ID: | CH004589 |
| Num Factors: | 2 |
| Num Metabolites: | 2094 |
| Units: | peak area |
