Journal Article

DKFZ-2023-00263

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling.

Altea-Manzano, P. ; Doglioni, G. ; Liu, Y. ; Cuadros, A. M. ; Nolan, E. ; Fernández-García, J. ; Wu, Q. ; Planque, M. ; Laue, K. J. ; Cidre-Aranaz, F.DKFZ* ; Liu, X.-Z. ; Marin-Bejar, O. ; Van Elsen, J. ; Vermeire, I. ; Broekaert, D. ; Demeyer, S. ; Spotbeen, X. ; Idkowiak, J. ; Montagne, A. ; Demicco, M. ; Alkan, H. F. ; Rabas, N. ; Riera-Domingo, C. ; Richard, F. ; Geukens, T. ; De Schepper, M. ; Leduc, S. ; Hatse, S. ; Lambrechts, Y. ; Kay, E. J. ; Lilla, S. ; Alekseenko, A. ; Geldhof, V. ; Boeckx, B. ; de la Calle Arregui, C. ; Floris, G. ; Swinnen, J. V. ; Marine, J.-C. ; Lambrechts, D. ; Pelechano, V. ; Mazzone, M. ; Zanivan, S. ; Cools, J. ; Wildiers, H. ; Baud, V. ; Grünewald, T.DKFZ* ; Ben-David, U. ; Desmedt, C. ; Malanchi, I. ; Fendt, S.-M.

2023
Nature Research London

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Please use a persistent id in citations: doi:10.1038/s43018-023-00513-2

Abstract: 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.

Note: 2023 Mar;4(3):344-364

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Contributing Institute(s):

1. Translationale Pädiatrische Sarkomforschung (B410)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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