TY  - JOUR
AU  - Altea-Manzano, Patricia
AU  - Doglioni, Ginevra
AU  - Liu, Yawen
AU  - Cuadros, Alejandro M
AU  - Nolan, Emma
AU  - Fernández-García, Juan
AU  - Wu, Qi
AU  - Planque, Mélanie
AU  - Laue, Kathrin Julia
AU  - Cidre-Aranaz, Florencia
AU  - Liu, Xiao-Zheng
AU  - Marin-Bejar, Oskar
AU  - Van Elsen, Joke
AU  - Vermeire, Ines
AU  - Broekaert, Dorien
AU  - Demeyer, Sofie
AU  - Spotbeen, Xander
AU  - Idkowiak, Jakub
AU  - Montagne, Aurélie
AU  - Demicco, Margherita
AU  - Alkan, H Furkan
AU  - Rabas, Nick
AU  - Riera-Domingo, Carla
AU  - Richard, François
AU  - Geukens, Tatjana
AU  - De Schepper, Maxim
AU  - Leduc, Sophia
AU  - Hatse, Sigrid
AU  - Lambrechts, Yentl
AU  - Kay, Emily Jane
AU  - Lilla, Sergio
AU  - Alekseenko, Alisa
AU  - Geldhof, Vincent
AU  - Boeckx, Bram
AU  - de la Calle Arregui, Celia
AU  - Floris, Giuseppe
AU  - Swinnen, Johannes V
AU  - Marine, Jean-Christophe
AU  - Lambrechts, Diether
AU  - Pelechano, Vicent
AU  - Mazzone, Massimiliano
AU  - Zanivan, Sara
AU  - Cools, Jan
AU  - Wildiers, Hans
AU  - Baud, Véronique
AU  - Grünewald, Thomas
AU  - Ben-David, Uri
AU  - Desmedt, Christine
AU  - Malanchi, Ilaria
AU  - Fendt, Sarah-Maria
TI  - A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling.
JO  - Nature cancer
VL  - 4
IS  - 3
SN  - 2662-1347
CY  - London
PB  - Nature Research
M1  - DKFZ-2023-00263
SP  - 344-364
PY  - 2023
N1  - 2023 Mar;4(3):344-364
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:36732635
DO  - DOI:10.1038/s43018-023-00513-2
UR  - https://inrepo02.dkfz.de/record/241155
ER  -