Thyroid hormone receptor beta signaling is a targetable driver of prostate cancer growth

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F25%3A00143639" target="_blank" >RIV/00216224:14740/25:00143639 - isvavai.cz</a>

Výsledek na webu

<a href="https://link.springer.com/article/10.1186/s12943-025-02451-2?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=clarivate" target="_blank" >https://link.springer.com/article/10.1186/s12943-025-02451-2?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=clarivate</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12943-025-02451-2" target="_blank" >10.1186/s12943-025-02451-2</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Thyroid hormone receptor beta signaling is a targetable driver of prostate cancer growth

Popis výsledku v původním jazyce

Thyroid hormone (TH) signaling plays a major role in the development, energy homeostasis, and metabolism of most tissues. Recent studies have identified THs as drivers of prostate cancer (PCa) development and progression. We reported that the T3-scavenger protein mu -crystallin (CRYM) regulates the development and progression of PCa and that this involved crosstalk with androgen receptor (AR) signaling. However, the mechanisms remain incompletely understood. Here, we explored the role of thyroid hormone receptor beta (TR beta), which is the main effector of TH signaling, in the context of PCa. The use of the TR beta-selective antagonist NH-3 inhibited PCa cell proliferation in vitro and reduced tumor size in PCa xenograft models in vivo. Notably, NH-3 was highly effective in the engrafted 22Rv1 cell line, a model for castration-resistant PCa (CRPC). Mechanistic studies revealed that NH-3 downregulates AR and the AR target genes Nkx3.1 and KLK3 (PSA). NH-3 was a more effective anticancer agent than enzalutamide, and their combined use was synergistic. Evidence from human datasets corroborates our findings, whereby elevated TR beta expression and mutations in the TH signaling pathway are associated with the onset of PCa. Collectively, these results establish TR beta as a mediator of tumorigenesis in PCa and identify NH-3 as a promising therapeutic agent for targeting AR signaling, particularly in CRPC.

Název v anglickém jazyce

Thyroid hormone receptor beta signaling is a targetable driver of prostate cancer growth

Popis výsledku anglicky

Thyroid hormone (TH) signaling plays a major role in the development, energy homeostasis, and metabolism of most tissues. Recent studies have identified THs as drivers of prostate cancer (PCa) development and progression. We reported that the T3-scavenger protein mu -crystallin (CRYM) regulates the development and progression of PCa and that this involved crosstalk with androgen receptor (AR) signaling. However, the mechanisms remain incompletely understood. Here, we explored the role of thyroid hormone receptor beta (TR beta), which is the main effector of TH signaling, in the context of PCa. The use of the TR beta-selective antagonist NH-3 inhibited PCa cell proliferation in vitro and reduced tumor size in PCa xenograft models in vivo. Notably, NH-3 was highly effective in the engrafted 22Rv1 cell line, a model for castration-resistant PCa (CRPC). Mechanistic studies revealed that NH-3 downregulates AR and the AR target genes Nkx3.1 and KLK3 (PSA). NH-3 was a more effective anticancer agent than enzalutamide, and their combined use was synergistic. Evidence from human datasets corroborates our findings, whereby elevated TR beta expression and mutations in the TH signaling pathway are associated with the onset of PCa. Collectively, these results establish TR beta as a mediator of tumorigenesis in PCa and identify NH-3 as a promising therapeutic agent for targeting AR signaling, particularly in CRPC.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

—

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular Cancer

ISSN

1476-4598

e-ISSN

1476-4598

Svazek periodika

24

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

21

Strana od-do

1-21

Kód UT WoS článku

001594409100001

EID výsledku v databázi Scopus

2-s2.0-105018653603