Stat5 induces androgen receptor (AR) gene transcription in prostate cancer and offers a druggable pathway to target AR signaling. Sci Adv 2024 Mar;10(9):eadi2742
Date
02/28/2024Pubmed ID
38416822Pubmed Central ID
PMC10901378DOI
10.1126/sciadv.adi2742Scopus ID
2-s2.0-85186741721 (requires institutional sign-in at Scopus site)Abstract
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.
Author List
Maranto C, Sabharwal L, Udhane V, Pitzen SP, McCluskey B, Qi S, O'Connor C, Devi S, Johnson S, Jacobsohn K, Banerjee A, Iczkowski KA, Wang L, Dehm SM, Nevalainen MTAuthor
Anjishnu Banerjee PhD Associate Professor in the Institute for Health and Equity department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cell Line, TumorGene Expression Regulation, Neoplastic
Humans
Male
Prostatic Neoplasms, Castration-Resistant
Receptors, Androgen
Signal Transduction
Transcription, Genetic
