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

Details

Serval ID
serval:BIB_3B2A745CA757
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sustained androgen receptor signaling is a determinant of melanoma cell growth potential and tumorigenesis.
Journal
The Journal of experimental medicine
Author(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
Publication state
Published
Issued date
01/02/2021
Peer-reviewed
Oui
Volume
218
Number
2
Pages
e20201137
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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
Open Access
Yes
Create date
02/11/2020 12:33
Last modification date
06/11/2020 6:26
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