Summary of project PR002249
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
| 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 |
Summary of all studies in project PR002249
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003637 | lomitapide effects on lipidomics | Homo sapiens | Pennsylvania State University | MS | 2025-09-29 | 1 | 6 | Uploaded data (6.7M)* |
| ST003638 | The effects of cystine limitation stress adaptation (CLSA) on metabolomics changes in pancreatic cancer cells (MiaPaCa-2) | Homo sapiens | Pennsylvania State University | MS | 2025-09-29 | 1 | 6 | Uploaded data (1.6M)* |
| ST003665 | The effects of cystine limitation stress adaptation (CLSA) on metabolomics changes in pancreatic cancer cells (PANC1) | Homo sapiens | Pennsylvania State University | MS | 2025-09-29 | 1 | 6 | Uploaded data (1.5M)* |
| ST003678 | The effects of cystine limitation stress adaptation (CLSA) on lipidomics changes in pancreatic cancer cells | Homo sapiens | Pennsylvania State University | MS | 2025-09-29 | 1 | 6 | Uploaded data (562.3M)* |
| ST003694 | FOLFIRINOX effects on lipidomics in pancreatic cancer cells | Homo sapiens | Pennsylvania State University | MS | 2025-09-29 | 1 | 6 | Uploaded data (10.1M)* |
