ZIP9 Is a Druggable Determinant of Sex Differences in Melanoma.

ABSTRACT: Melanoma and most other cancers occur more frequently and have worse prognosis in males compared with females. Although sex steroids are thought to be involved, classical androgen and estrogen receptors are not detectable in most melanomas. Here we show that testosterone promotes melanoma proliferation by activating ZIP9 (SLC39A9), a zinc transporter that is widely expressed in human melanoma but not intentionally targeted by available therapeutics. This testosterone activity required an influx of zinc, activation of MAPK, and nuclear translocation of YAP. FDA-approved inhibitors of the classical androgen receptor also inhibited ZIP9, thereby antagonizing the protumorigenic effects of testosterone in melanoma. In male mice, androgen receptor inhibitors suppressed growth of ZIP9-expressing

SUBMITTER: Aguirre-Portoles C 

PROVIDER: S-EPMC8977092 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature