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This article is the author's final published version in Science Advances, Volume 10, Issue 9. March 2024, Article number eadi2742.

The published version is available at Copyright © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science.


Androgen receptor (AR) drives prostate cancer (PC) growth and progression, and targeting AR signaling is the mainstay of pharmacological therapies for PC. Resistance develops relatively fast as a result of refueled AR activity. A major gap in the field is the lack of understanding of targetable mechanisms that induce persistent AR expression in castrate-resistant PC (CRPC). This study uncovers an unexpected function of active Stat5 signaling, a known promoter of PC growth and clinical progression, as a potent inducer of AR gene transcription. Stat5 suppression inhibited AR gene transcription in preclinical PC models and reduced the levels of wild-type, mutated, and truncated AR proteins. Pharmacological Stat5 inhibition by a specific small-molecule Stat5 inhibitor down-regulated Stat5-inducible genes as well as AR and AR-regulated genes and suppressed PC growth. This work introduces the concept of Stat5 as an inducer of AR gene transcription in PC. Pharmacological Stat5 inhibitors may represent a new strategy for suppressing AR and CRPC growth.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Figs. S1 to S7; Tables S1 and S2; Legends for data files S1 to S8.pdf (4602 kB)
Figs. S1 to S7; Tables S1 and S2; Legends for data files S1 to S8

Data files S1 to (2175 kB)
Data files S1 to S8