Journal Article

DKFZ-2023-01942

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.

Taylor, J. (First author)DKFZ* ; Uhl, L.DKFZ* ; Moll, I.DKFZ* ; Hasan, S. S.DKFZ* ; Wiedmann, L.DKFZ* ; Morgenstern, J. ; Giaimo, B. D. ; Friedrich, T. ; Alsina-Sanchis, E.DKFZ* ; De Angelis Rigotti, F.DKFZ* ; Mülfarth, R.DKFZ* ; Kaltenbach, S. ; Schenk, D.DKFZ* ; Nickel, F. ; Fleming, T. ; Sprinzak, D. ; Mogler, C. ; Korff, T. ; Billeter, A. T. ; Müller-Stich, B. P. ; Berriel Diaz, M. ; Borggrefe, T. ; Herzig, S. ; Rohm, M. ; Rodriguez-Vita, J.DKFZ* ; Fischer, A. (Last author)DKFZ*

2023
Nature Research London

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s43018-023-00622-y

Abstract: Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors. Considering that the continuous endothelium in WAT is the first line of contact with circulating factors, we postulated whether the endothelium itself may orchestrate tissue remodeling. Here, we show using human and mouse cancer models that during precachexia, tumors overactivate Notch1 signaling in distant WAT endothelium. Sustained endothelial Notch1 signaling induces a WAT wasting phenotype in male mice through excessive retinoic acid production. Pharmacological blockade of retinoic acid signaling was sufficient to inhibit WAT wasting in a mouse cancer cachexia model. This demonstrates that cancer manipulates the endothelium at distant sites to mediate WAT wasting by altering angiocrine signals.

Note: #EA:A270#LA:A270# / 2023 Nov;4(11):1544-1560

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Contributing Institute(s):

1. A270 Vaskuläre Signaltransduktion und Krebs (A270)

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 - Clinical Medicine ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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