Ma, Min; Ghosh, Soumitra; Tavernari, Daniele; Katarkar, Atul; Clocchiatti, Andrea; Mazzeo, Luigi; Samarkina, Anastasia; Epiney, Justine; Yu, Yi-Ru; Ho, Ping-Chih; Levesque, Mitchell P; Özdemir, Berna C.; Ciriello, Giovanni; Dummer, Reinhard; Dotto, G Paolo (2021). Sustained androgen receptor signaling is a determinant of melanoma cell growth potential and tumorigenesis. The Journal of experimental medicine, 218(2) Rockefeller Univ. Press 10.1084/jem.20201137
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology |
UniBE Contributor: |
Özdemir, Berna |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1540-9538 |
Publisher: |
Rockefeller Univ. Press |
Language: |
English |
Submitter: |
Rebeka Gerber |
Date Deposited: |
24 Nov 2021 09:53 |
Last Modified: |
05 Dec 2022 15:54 |
Publisher DOI: |
10.1084/jem.20201137 |
PubMed ID: |
33112375 |
BORIS DOI: |
10.48350/160868 |
URI: |
https://boris.unibe.ch/id/eprint/160868 |
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