Summary of Study ST003898
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 PR002439. The data can be accessed directly via it's Project DOI: 10.21228/M8CG2W 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 | ST003898 |
| Study Title | Glycosaminoglycan-mediated lipoprotein uptake protects cancer cells from ferroptosis |
| Study Summary | Lipids are essential components of cancer cells due to their structural and signaling roles and many cancers take up extracellular lipids to meet metabolic demands. How these lipids contribute to cancer growth and progression remains poorly understood. Using functional genetic screens, lipoprotein uptake—the primary mechanism for lipid transport in circulation—is identify as a key determinant of ferroptosis sensitivity in cancer. Lipoprotein supplementation robustly inhibits ferroptosis across numerous cancer types, an effect largely driven by lipoprotein delivery of α-tocopherol. Mechanistically, cancer cells take up lipoproteins through a pathway dependent on sulfated glycosaminoglycans (GAGs) linked to cell-surface proteoglycans. Disrupting GAG biosynthesis or acutely degrading surface GAGs reduces lipoprotein uptake, sensitizes cancer cells to ferroptosis, and impairs tumor growth in mice. Notably, human clear cell renal cell carcinomas (ccRCC), a lipid-rich malignancy, exhibit elevated levels of chondroitin sulfate and increased lipoprotein-derived α-tocopherol compared to normal kidney tissue. Altogether, this work establishes lipoprotein uptake as a critical anti-ferroptotic mechanism in cancer and implicates GAG biosynthesis as a therapeutic target. |
| Institute | University of Texas Southwestern Medical Center at Dallas |
| Department | Children's Research Institute |
| Laboratory | Metabolomics Facility |
| Last Name | Cai |
| First Name | Feng |
| Address | 6000 Harry Hines Blvd. |
| feng.cai@utsouthwestern.edu | |
| Phone | 2146483056 |
| Submit Date | 2025-04-24 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-05-08 |
| Release Version | 1 |
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Project:
| Project ID: | PR002439 |
| Project DOI: | doi: 10.21228/M8CG2W |
| Project Title: | Measuring α-tocopherol and cholesterol from ccRCC tissues |
| Project Summary: | Lipids are essential components of cancer cells due to their structural and signaling roles. To meet metabolic demands, many cancers take up extracellular lipids; however, how these lipids contribute to cancer growth and progression remains poorly understood. Here, using functional genetic screens, we identify lipoprotein uptake—the primary mechanism for lipid transport in circulation—as a key determinant of ferroptosis sensitivity in cancer. Lipoprotein supplementation robustly inhibits ferroptosis across numerous cancer types, an effect largely driven by lipoprotein delivery of α-tocopherol, the most abundant form of vitamin E. Mechanistically, cancer cells take up lipoproteins through a pathway dependent on sulfated glycosaminoglycans (GAGs) linked to cell-surface proteoglycans. Disrupting GAG biosynthesis or acutely degrading surface GAGs reduces lipoprotein uptake, sensitizes cancer cells to ferroptosis, and impairs tumour growth in mice. Notably, human clear cell renal cell carcinomas (ccRCC), a lipid-rich malignancy, exhibit elevated levels of chondroitin sulfate and increased lipoprotein-derived α-tocopherol compared to normal kidney tissue. Altogether, our work establishes lipoprotein uptake as a critical anti-ferroptotic mechanism in cancer and implicates GAG biosynthesis as a therapeutic target. |
| Institute: | University of Texas Southwestern Medical Center at Dallas |
| Department: | Children's Research Institute |
| Laboratory: | Metabolomics Facility |
| Last Name: | Cai |
| First Name: | Feng |
| Address: | 6000 Harry Hines Blvd. |
| Email: | feng.cai@utsouthwestern.edu |
| Phone: | 2146483056 |
