%0 Journal Article
%A Altea-Manzano, Patricia
%A Doglioni, Ginevra
%A Liu, Yawen
%A Cuadros, Alejandro M
%A Nolan, Emma
%A Fernández-García, Juan
%A Wu, Qi
%A Planque, Mélanie
%A Laue, Kathrin Julia
%A Cidre-Aranaz, Florencia
%A Liu, Xiao-Zheng
%A Marin-Bejar, Oskar
%A Van Elsen, Joke
%A Vermeire, Ines
%A Broekaert, Dorien
%A Demeyer, Sofie
%A Spotbeen, Xander
%A Idkowiak, Jakub
%A Montagne, Aurélie
%A Demicco, Margherita
%A Alkan, H Furkan
%A Rabas, Nick
%A Riera-Domingo, Carla
%A Richard, François
%A Geukens, Tatjana
%A De Schepper, Maxim
%A Leduc, Sophia
%A Hatse, Sigrid
%A Lambrechts, Yentl
%A Kay, Emily Jane
%A Lilla, Sergio
%A Alekseenko, Alisa
%A Geldhof, Vincent
%A Boeckx, Bram
%A de la Calle Arregui, Celia
%A Floris, Giuseppe
%A Swinnen, Johannes V
%A Marine, Jean-Christophe
%A Lambrechts, Diether
%A Pelechano, Vicent
%A Mazzone, Massimiliano
%A Zanivan, Sara
%A Cools, Jan
%A Wildiers, Hans
%A Baud, Véronique
%A Grünewald, Thomas
%A Ben-David, Uri
%A Desmedt, Christine
%A Malanchi, Ilaria
%A Fendt, Sarah-Maria
%T A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling.
%J Nature cancer
%V 4
%N 3
%@ 2662-1347
%C London
%I Nature Research
%M DKFZ-2023-00263
%P 344-364
%D 2023
%Z 2023 Mar;4(3):344-364
%X Metabolic rewiring is often considered an adaptive pressure limiting metastasis formation; however, some nutrients available at distant organs may inherently promote metastatic growth. We find that the lung and liver are lipid-rich environments. Moreover, we observe that pre-metastatic niche formation increases palmitate availability only in the lung, whereas a high-fat diet increases it in both organs. In line with this, targeting palmitate processing inhibits breast cancer-derived lung metastasis formation. Mechanistically, breast cancer cells use palmitate to synthesize acetyl-CoA in a carnitine palmitoyltransferase 1a-dependent manner. Concomitantly, lysine acetyltransferase 2a expression is promoted by palmitate, linking the available acetyl-CoA to the acetylation of the nuclear factor-kappaB subunit p65. Deletion of lysine acetyltransferase 2a or carnitine palmitoyltransferase 1a reduces metastasis formation in lean and high-fat diet mice, and lung and liver metastases from patients with breast cancer show coexpression of both proteins. In conclusion, palmitate-rich environments foster metastases growth by increasing p65 acetylation, resulting in a pro-metastatic nuclear factor-kappaB signaling.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36732635
%R 10.1038/s43018-023-00513-2
%U https://inrepo02.dkfz.de/record/241155