Dietary palmitic acid promotes a prometastatic memory via Schwann cells

Gloria Pascual (), Diana Domínguez, Marc Elosúa-Bayes, Felipe Beckedorff, Carmelo Laudanna, Claudia Bigas, Delphine Douillet, Carolina Greco, Aikaterini Symeonidi, Inmaculada Hernández, Sara Ruiz Gil, Neus Prats, Coro Bescós, Ramin Shiekhattar, Moran Amit, Holger Heyn, Ali Shilatifard () and Salvador Aznar Benitah ()
Additional contact information
Gloria Pascual: The Barcelona Institute of Science and Technology (BIST)
Diana Domínguez: The Barcelona Institute of Science and Technology (BIST)
Marc Elosúa-Bayes: Barcelona Institute of Science and Technology (BIST)
Felipe Beckedorff: University of Miami Miller School of Medicine
Carmelo Laudanna: The Barcelona Institute of Science and Technology (BIST)
Claudia Bigas: The Barcelona Institute of Science and Technology (BIST)
Delphine Douillet: Northwestern University Feinberg School of Medicine
Carolina Greco: University of California
Aikaterini Symeonidi: The Barcelona Institute of Science and Technology (BIST)
Inmaculada Hernández: The Barcelona Institute of Science and Technology (BIST)
Sara Ruiz Gil: Barcelona Institute of Science and Technology (BIST)
Neus Prats: The Barcelona Institute of Science and Technology (BIST)
Coro Bescós: Universitat Autònoma de Barcelona
Ramin Shiekhattar: University of Miami Miller School of Medicine
Moran Amit: The University of Texas MD Anderson Cancer Center
Holger Heyn: Barcelona Institute of Science and Technology (BIST)
Ali Shilatifard: Northwestern University Feinberg School of Medicine
Salvador Aznar Benitah: The Barcelona Institute of Science and Technology (BIST)

Nature, 2021, vol. 599, issue 7885, 485-490

Abstract: Abstract Fatty acid uptake and altered metabolism constitute hallmarks of metastasis1,2, yet evidence of the underlying biology, as well as whether all dietary fatty acids are prometastatic, is lacking. Here we show that dietary palmitic acid (PA), but not oleic acid or linoleic acid, promotes metastasis in oral carcinomas and melanoma in mice. Tumours from mice that were fed a short-term palm-oil-rich diet (PA), or tumour cells that were briefly exposed to PA in vitro, remained highly metastatic even after being serially transplanted (without further exposure to high levels of PA). This PA-induced prometastatic memory requires the fatty acid transporter CD36 and is associated with the stable deposition of histone H3 lysine 4 trimethylation by the methyltransferase Set1A (as part of the COMPASS complex (Set1A/COMPASS)). Bulk, single-cell and positional RNA-sequencing analyses indicate that genes with this prometastatic memory predominantly relate to a neural signature that stimulates intratumoural Schwann cells and innervation, two parameters that are strongly correlated with metastasis but are aetiologically poorly understood3,4. Mechanistically, tumour-associated Schwann cells secrete a specialized proregenerative extracellular matrix, the ablation of which inhibits metastasis initiation. Both the PA-induced memory of this proneural signature and its long-term boost in metastasis require the transcription factor EGR2 and the glial-cell-stimulating peptide galanin. In summary, we provide evidence that a dietary metabolite induces stable transcriptional and chromatin changes that lead to a long-term stimulation of metastasis, and that this is related to a proregenerative state of tumour-activated Schwann cells.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-021-04075-0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

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:nature:v:599:y:2021:i:7885:d:10.1038_s41586-021-04075-0

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

DOI: 10.1038/s41586-021-04075-0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

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