Summary of project PR002307
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 PR002307. The data can be accessed directly via it's Project DOI: 10.21228/M8F244 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002307 |
| Project DOI: | doi: 10.21228/M8F244 |
| Project Title: | Microenvironmental arginine restriction sensitizes pancreatic cancers to polyunsaturated fatty acids by suppression of lipid synthesis |
| Project Type: | Lipidomics |
| Project Summary: | Nutrient limitation is a characteristic feature of poorly perfused tumors. These changes in nutrient availability impose metabolic constraints and perturb metabolic pathways in cancer cells, in contrast to cells in well-perfused tissues. Consequently, targeting the metabolic dependencies created by tumor microenvironmental constraints may be a promising antineoplastic therapeutic approach. To identify these adaptations, we challenged pancreatic cancer cell lines (mouse Pancreatic Ductal Adenocarcinoma - PDAC) with pathophysiological nutrient levels and analyzed changes to cell metabolism. Here, we report that arginine limitation in pancreatic cancer perturbs saturated and monounsaturated fatty acid synthesis by suppressing the lipogenic transcription factor SREBP1. Synthesis of these acyl species is critical to maintaining a balance of saturated, monounsaturated, and polyunsaturated fatty acids in cellular membranes. We found that, as a consequence of the loss of fatty acid synthesis, pancreatic cancer cells were unable to maintain balanced lipidomes when exposed to polyunsaturated fatty acids, leading to cell death by ferroptosis. Importantly, we found orally administering oils rich in polyunsaturated fats reduces tumor burden in mice with pancreatic cancer. In sum, this study illustrates that arginine restriction in the tumor microenvironment alters pancreatic cancer cells by perturbing lipid synthesis, making them sensitive to supplementation with polyunsaturated fats. |
| Institute: | University of Chicago |
| Last Name: | Jonker |
| First Name: | Patrick |
| Address: | 929 E 57th St. Chicago IL, 60637 |
| Email: | pbjonker@uchicago.edu |
| Phone: | 6162884547 |
Summary of all studies in project PR002307
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003714 | Lipidomics analysis of mouse PDAC cell lines treated with alpha-eleostearic acid | Mus musculus | University of Chicago | MS | 2025-02-14 | 1 | 18 | Uploaded data (5.5G)* |
| ST003715 | Lipidomics analysis of mouse PDAC cell lines treated with tung oil | Mus musculus | University of Chicago | MS | 2025-02-14 | 1 | 18 | Uploaded data (5.5G)* |
| ST003716 | Lipidomics analysis of mice treated with tung or safflower oil by oral gavage. | Mus musculus | University of Chicago | MS | 2025-02-14 | 1 | 24 | Uploaded data (13.2G)* |
| ST003717 | Lipidomics analysis of mouse pancreatic cancer cells cultured RPMI, TIFM, or TIFM + arginine under lipid deprivation | Mus musculus | University of Chicago | MS | 2025-02-14 | 1 | 18 | Uploaded data (5.6G)* |
| ST003718 | Metabolomics of plasma and tumor interstitial fluid (TIF) of tumors from Lyz2-Cre(+/+);Arg1(fl/fl) mice. | Mus musculus | University of Chicago | MS | 2025-02-14 | 1 | 22 | Uploaded data (306.7M)* |
