Cellular transformation promotes the incorporation of docosahexaenoic acid into the endolysosome-specific lipid bis(monoacylglycerol)phosphate in breast cancer.

Autor: Berg AL; Department of Biochemistry and Molecular Medicine and UC Davis Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA., Showalter MR; West Coast Metabolomics Center, UC Davis Genome Center, University of California Davis, Davis, CA, USA., Kosaisawe N; Department of Molecular and Cellular Biology, University of California Davis, Davis, CA, USA., Hu M; Department of Biochemistry and Molecular Medicine and UC Davis Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA., Stephens NC; West Coast Metabolomics Center, UC Davis Genome Center, University of California Davis, Davis, CA, USA., Sa M; West Coast Metabolomics Center, UC Davis Genome Center, University of California Davis, Davis, CA, USA., Heil H; West Coast Metabolomics Center, UC Davis Genome Center, University of California Davis, Davis, CA, USA., Castro N; Department of Biochemistry and Molecular Medicine and UC Davis Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA., Chen JJ; Department of Biochemistry and Molecular Medicine and UC Davis Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA., VanderVorst K; Department of Biochemistry and Molecular Medicine and UC Davis Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA., Wheeler MR; Department of Biochemistry and Molecular Medicine and UC Davis Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA., Rabow Z; West Coast Metabolomics Center, UC Davis Genome Center, University of California Davis, Davis, CA, USA., Cajka T; West Coast Metabolomics Center, UC Davis Genome Center, University of California Davis, Davis, CA, USA; Institute of Physiology of the Czech Academy of Sciences, Prague, 14200, Czech Republic., Albeck J; Department of Molecular and Cellular Biology, University of California Davis, Davis, CA, USA., Fiehn O; West Coast Metabolomics Center, UC Davis Genome Center, University of California Davis, Davis, CA, USA., Carraway KL 3rd; Department of Biochemistry and Molecular Medicine and UC Davis Comprehensive Cancer Center, University of California Davis School of Medicine, Sacramento, CA, USA. Electronic address: klcarraway@ucdavis.edu.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2023 Mar 31; Vol. 557, pp. 216090. Date of Electronic Publication: 2023 Feb 10.
DOI: 10.1016/j.canlet.2023.216090
Abstrakt: Bis(monoacylglycero)phosphates (BMPs), a class of lipids highly enriched within endolysosomal organelles, are key components of the lysosomal intraluminal vesicles responsible for activating sphingolipid catabolic enzymes. While BMPs are understudied relative to other phospholipids, recent reports associate BMP dysregulation with a variety of pathological states including neurodegenerative diseases and lysosomal storage disorders. Since the dramatic lysosomal remodeling characteristic of cellular transformation could impact BMP abundance and function, we employed untargeted lipidomics approaches to identify and quantify BMP species in several in vitro and in vivo models of breast cancer and comparative non-transformed cells and tissues. We observed lower BMP levels within transformed cells relative to normal cells, and consistent enrichment of docosahexaenoic acid (22:6) fatty acyl chain-containing BMP species in both human- and mouse-derived mammary tumorigenesis models. Our functional analysis points to a working model whereby 22:6 BMPs serve as reactive oxygen species scavengers in tumor cells, protecting lysosomes from oxidant-induced lysosomal membrane permeabilization. Our findings suggest that breast tumor cells might divert polyunsaturated fatty acids into BMP lipids as part of an adaptive response to protect their lysosomes from elevated reactive oxygen species levels, and raise the possibility that BMP-mediated lysosomal protection is a tumor-specific vulnerability that may be exploited therapeutically.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kermit Carraway reports financial support was provided by National Institutes of Health. Oliver Fiehn reports financial support was provided by National Institutes of Health.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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