Journal article
Fatty acid synthase-derived lipid stores support breast cancer metastasis
Cancer & metabolism, Vol.13(1), 35
07/10/2025
DOI: 10.1186/s40170-025-00404-3
PMCID: PMC12247306
PMID: 40640944
Abstract
Lipid accumulation is associated with breast cancer metastasis. However, the mechanisms underlying how breast cancer cells increase lipid stores and their functional role in disease progression remain incompletely understood. Herein we quantified changes in lipid metabolism and characterized cytoplasmic lipid droplets in metastatic versus non-metastatic breast cancer cells.
C-labeled palmitate was used to determine differences in fatty acid (FA) uptake and oxidation. Despite similar levels of palmitate uptake, metastatic cells increase lipid accumulation and oxidation of endogenous FAs compared to non-metastatic cells. Isotope tracing also demonstrated that metastatic cells support increased de novo lipogenesis by converting higher levels of glutamine and glucose into the FA precursor, citrate. Consistent with this, metastatic cells displayed increased levels of fatty acid synthase (FASN) and de novo lipogenesis. Genetic depletion or pharmacologic inhibition of FASN reduced cell migration, survival in anoikis assays, and in vivo metastasis. Finally, global proteomic analysis indicated that proteins involved in proteasome function, mitotic cell cycle, and intracellular protein transport were reduced following FASN inhibition of metastatic cells. Overall, these studies demonstrate that breast cancer metastases accumulate FAs by increasingde novo lipogenesis, storing TAG as cytoplasmic lipid droplets, and catabolizing these stores to drive several FAO-dependent steps in metastasis.
Details
- Title: Subtitle
- Fatty acid synthase-derived lipid stores support breast cancer metastasis
- Creators
- Chaylen Andolino - Purdue University West LafayetteEylem Kulkoyluoglu Cotul - Purdue University West LafayetteZilin Xianyu - Purdue University West LafayetteYun Li - University of IowaDivya Bhat - University of IowaMitchell Ayers - Purdue University West LafayetteKimberly K Buhman - Purdue University West LafayetteStephen D Hursting - University of North Carolina at Chapel HillMichael K Wendt - University of IowaDorothy Teegarden - Purdue University West Lafayette
- Resource Type
- Journal article
- Publication Details
- Cancer & metabolism, Vol.13(1), 35
- DOI
- 10.1186/s40170-025-00404-3
- PMID
- 40640944
- PMCID
- PMC12247306
- NLM abbreviation
- Cancer Metab
- ISSN
- 2049-3002
- eISSN
- 2049-3002
- Publisher
- BMC
- Grant note
- #TR000006 / NIH/NCRR R01CA232589 / NIH HHS
- Language
- English
- Date published
- 07/10/2025
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984845450502771
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