Journalartikel
Autorenliste: Taylor, Jacqueline; Uhl, Leonie; Moll, Iris; Hasan, Sana Safatul; Wiedmann, Lena; Morgenstern, Jakob; Giaimo, Benedetto Daniele; Friedrich, Tobias; Alsina-Sanchis, Elisenda; Rigotti, Francesca De Angelis; Mulfarth, Ronja; Kaltenbach, Sarah; Schenk, Darius; Nickel, Felix; Fleming, Thomas; Sprinzak, David; Mogler, Carolin; Korff, Thomas; Billeter, Adrian T.; Muller-Stich, Beat P.; Diaz, Mauricio Berriel; Borggrefe, Tilman; Herzig, Stephan; Rohm, Maria; Rodriguez-Vita, Juan; Fischer, Andreas
Jahr der Veröffentlichung: 2023
Seiten: 1544-1560
Zeitschrift: Nature Cancer
Bandnummer: 4
Heftnummer: 11
eISSN: 2662-1347
Open Access Status: Hybrid
DOI Link: https://doi.org/10.1038/s43018-023-00622-y
Verlag: Nature Research
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.
Abstract:
Zitierstile
Harvard-Zitierstil: Taylor, J., Uhl, L., Moll, I., Hasan, S., Wiedmann, L., Morgenstern, J., et al. (2023) Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia, Nature Cancer, 4(11), pp. 1544-1560. https://doi.org/10.1038/s43018-023-00622-y
APA-Zitierstil: Taylor, J., Uhl, L., Moll, I., Hasan, S., Wiedmann, L., Morgenstern, J., Giaimo, B., Friedrich, T., Alsina-Sanchis, E., Rigotti, F., Mulfarth, R., Kaltenbach, S., Schenk, D., Nickel, F., Fleming, T., Sprinzak, D., Mogler, C., Korff, T., Billeter, A., ...Fischer, A. (2023). Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia. Nature Cancer. 4(11), 1544-1560. https://doi.org/10.1038/s43018-023-00622-y
Schlagwörter
BLOCKADE; IL-33; THERMOGENESIS
