Caveolin-1-mediated sphingolipid oncometabolism underlies a metabolic vulnerability of prostate cancer

Jody Vykoukal, Johannes F. Fahrmann, Justin R. Gregg, Zhe Tang, Spyridon Basourakos, Ehsan Irajizad, Sanghee Park, Guang Yang, Chad J. Creighton, Alia Fleury, Jeffrey Mayo, Adriana Paulucci-Holthauzen, Jennifer B. Dennison, Eunice Murage, Christine B. Peterson, John W. Davis, Jeri Kim (), Samir Hanash () and Timothy C. Thompson ()
Additional contact information
Jody Vykoukal: The University of Texas MD Anderson Cancer Center
Johannes F. Fahrmann: The University of Texas MD Anderson Cancer Center
Justin R. Gregg: The University of Texas MD Anderson Cancer Center
Zhe Tang: The University of Texas MD Anderson Cancer Center
Spyridon Basourakos: The University of Texas MD Anderson Cancer Center
Ehsan Irajizad: The University of Texas MD Anderson Cancer Center
Sanghee Park: The University of Texas MD Anderson Cancer Center
Guang Yang: The University of Texas MD Anderson Cancer Center
Chad J. Creighton: The University of Texas MD Anderson Cancer Center
Alia Fleury: The University of Texas MD Anderson Cancer Center
Jeffrey Mayo: The University of Texas MD Anderson Cancer Center
Adriana Paulucci-Holthauzen: The University of Texas MD Anderson Cancer Center
Jennifer B. Dennison: The University of Texas MD Anderson Cancer Center
Eunice Murage: The University of Texas MD Anderson Cancer Center
Christine B. Peterson: The University of Texas MD Anderson Cancer Center
John W. Davis: The University of Texas MD Anderson Cancer Center
Jeri Kim: The University of Texas MD Anderson Cancer Center
Samir Hanash: The University of Texas MD Anderson Cancer Center
Timothy C. Thompson: The University of Texas MD Anderson Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Plasma and tumor caveolin-1 (Cav-1) are linked with disease progression in prostate cancer. Here we report that metabolomic profiling of longitudinal plasmas from a prospective cohort of 491 active surveillance (AS) participants indicates prominent elevations in plasma sphingolipids in AS progressors that, together with plasma Cav-1, yield a prognostic signature for disease progression. Mechanistic studies of the underlying tumor supportive onco-metabolism reveal coordinated activities through which Cav-1 enables rewiring of cancer cell lipid metabolism towards a program of 1) exogenous sphingolipid scavenging independent of cholesterol, 2) increased cancer cell catabolism of sphingomyelins to ceramide derivatives and 3) altered ceramide metabolism that results in increased glycosphingolipid synthesis and efflux of Cav-1-sphingolipid particles containing mitochondrial proteins and lipids. We also demonstrate, using a prostate cancer syngeneic RM-9 mouse model and established cell lines, that this Cav-1-sphingolipid program evidences a metabolic vulnerability that is targetable to induce lethal mitophagy as an anti-tumor therapy.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-17645-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17645-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-17645-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().