Sustained androgen receptor signaling is a determinant of melanoma cell growth potential and tumorigenesis.

Détails

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Etat: Public
Version: de l'auteur
Licence: CC BY 4.0
ID Serval
serval:BIB_3B2A745CA757
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Sustained androgen receptor signaling is a determinant of melanoma cell growth potential and tumorigenesis.
Périodique
The Journal of experimental medicine
Auteur(s)
Ma M., Ghosh S., Tavernari D., Katarkar A., Clocchiatti A., Mazzeo L., Samarkina A., Epiney J., Yu Y.R., Ho P.C., Levesque M.P., Özdemir B.C., Ciriello G., Dummer R., Dotto G.P.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Statut éditorial
Publié
Date de publication
01/02/2021
Peer-reviewed
Oui
Volume
218
Numéro
2
Pages
e20201137
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Melanoma susceptibility differs significantly in male versus female populations. Low levels of androgen receptor (AR) in melanocytes of the two sexes are accompanied by heterogeneous expression at various stages of the disease. Irrespective of expression levels, genetic and pharmacological suppression of AR activity in melanoma cells blunts proliferation and induces senescence, while increased AR expression or activation exert opposite effects. AR down-modulation elicits a shared gene expression signature associated with better patient survival, related to interferon and cytokine signaling and DNA damage/repair. AR loss leads to dsDNA breakage, cytoplasmic leakage, and STING activation, with AR anchoring the DNA repair proteins Ku70/Ku80 to RNA Pol II and preventing RNA Pol II-associated DNA damage. AR down-modulation or pharmacological inhibition suppresses melanomagenesis, with increased intratumoral infiltration of macrophages and, in an immune-competent mouse model, cytotoxic T cells. AR provides an attractive target for improved management of melanoma independent of patient sex.
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/11/2020 13:33
Dernière modification de la notice
08/05/2021 6:32
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