Journal Article

DKFZ-2023-02790

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png p53 deficient breast cancer cells reprogram preadipocytes toward tumor-protective immunomodulatory cells.

Hassin, O. ; Sernik, M. ; Seligman, A. ; Vogel, F. C. E.DKFZ* ; Wellenstein, M. D. ; Smollich, J. ; Halperin, C. ; Pirona, A. C. ; Toledano, L. N. ; Caballero, C. D.DKFZ* ; Schlicker, L.DKFZ* ; Salame, T.-M. ; Sarusi Portuguez, A. ; Aylon, Y. ; Scherz-Shouval, R. ; Geiger, T. ; de Visser, K. E. ; Schulze, A.DKFZ* ; Oren, M.

2023
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.2311460120

Abstract: The TP53 gene is mutated in approximately 30% of all breast cancer cases. Adipocytes and preadipocytes, which constitute a substantial fraction of the stroma of normal mammary tissue and breast tumors, undergo transcriptional, metabolic, and phenotypic reprogramming during breast cancer development and play an important role in tumor progression. We report here that p53 loss in breast cancer cells facilitates the reprogramming of preadipocytes, inducing them to acquire a unique transcriptional and metabolic program that combines impaired adipocytic differentiation with augmented cytokine expression. This, in turn, promotes the establishment of an inflammatory tumor microenvironment, including increased abundance of Ly6C+ and Ly6G+ myeloid cells and elevated expression of the immune checkpoint ligand PD-L1. We also describe a potential gain-of-function effect of common p53 missense mutations on the inflammatory reprogramming of preadipocytes. Altogether, our study implicates p53 deregulation in breast cancer cells as a driver of tumor-supportive adipose tissue reprogramming, expanding the network of non-cell autonomous mechanisms whereby p53 dysfunction may promote cancer. Further elucidation of the interplay between p53 and adipocytes within the tumor microenvironment may suggest effective therapeutic targets for the treatment of breast cancer patients.

Keyword(s): adipocytes ; breast cancer ; p53 ; preadipocytes

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Contributing Institute(s):

1. Metabolismus und Microenvironment (A410)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; National-Konsortium ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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