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@ARTICLE{Taylor:283156,
author = {J. Taylor$^*$ and L. Uhl$^*$ and I. Moll$^*$ and S. S.
Hasan$^*$ and L. Wiedmann$^*$ and J. Morgenstern and B. D.
Giaimo and T. Friedrich and E. Alsina-Sanchis$^*$ and F. De
Angelis Rigotti$^*$ and R. Mülfarth$^*$ and S. Kaltenbach
and D. Schenk$^*$ and F. Nickel and T. Fleming and D.
Sprinzak and C. Mogler and T. Korff and A. T. Billeter and
B. P. Müller-Stich and M. Berriel Diaz and T. Borggrefe and
S. Herzig and M. Rohm and J. Rodriguez-Vita$^*$ and A.
Fischer$^*$},
title = {{E}ndothelial {N}otch1 signaling in white adipose tissue
promotes cancer cachexia.},
journal = {Nature cancer},
volume = {4},
number = {11},
issn = {2662-1347},
address = {London},
publisher = {Nature Research},
reportid = {DKFZ-2023-01942},
pages = {1544-1560},
year = {2023},
note = {#EA:A270#LA:A270# / 2023 Nov;4(11):1544-1560},
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.},
cin = {A270},
ddc = {610},
cid = {I:(DE-He78)A270-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37749321},
doi = {10.1038/s43018-023-00622-y},
url = {https://inrepo02.dkfz.de/record/283156},
}