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

J 2025

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

FESIUK, Aleksandra; Daniel POLOSKE; Elvin D. DE ARAUJO; Geordon A. FRERE; Timothy B. WRIGHT et al.

Základní údaje

Originální název

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

Autoři

FESIUK, Aleksandra; Daniel POLOSKE; Elvin D. DE ARAUJO; Geordon A. FRERE; Timothy B. WRIGHT; Gary TIN; Yasir S. RAOUF; Olasunkanmi O. OLAOYE; Ji Sung PARK; Nicolas BLAVET ; Boris TICHÝ ; Michaela SCHLEDERER; Sandra HOGLER; Michael WOLF; Cecile PHILIPPE; Osman AKSOY; Adam VARADY; Alejandro Antonio MEDAGLIA MATA; Maxim VARENICJA; Boglarka SZABO; Theresa WEISS; Gabriel WASINGER; Torben REDMER; Heidi A. NEUBAUER; Martin SUSANI; Clemens P. SPIELVOGEL; Jing NING; Maik DAHLHOFF; Martin SCHEPELMANN; Richard KENNEDY; Richard MORIGGL; Geoffrey BROWN; Jenny PERSSON; Christopher GERNER; Vojtěch BYSTRÝ; Oldamur HOLLOCZKI; David M. HEERY; Patrick T. GUNNING; Olaf MERKEL; Brigitte HANTUSCH a Lukas KENNER

Vydání

Molecular Cancer, LONDON, BioMed Central, 2025, 1476-4598

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 33.900 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

Thyroid hormone receptor beta; Prostate cancer; NH-3; Androgen receptor; Murine PCa model

Štítky

CF BIOIT, CF GEN, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 14. 3. 2026 20:09, Mgr. Eva Dubská

Anotace

V originále

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.

Návaznosti

90267, velká výzkumná infrastruktura

Název: NCMG III

Citovat

FESIUK, Aleksandra; Daniel POLOSKE; Elvin D. DE ARAUJO; Geordon A. FRERE; Timothy B. WRIGHT; Gary TIN; Yasir S. RAOUF; Olasunkanmi O. OLAOYE; Ji Sung PARK; Nicolas BLAVET; Boris TICHÝ; Michaela SCHLEDERER; Sandra HOGLER; Michael WOLF; Cecile PHILIPPE; Osman AKSOY; Adam VARADY; Alejandro Antonio MEDAGLIA MATA; Maxim VARENICJA; Boglarka SZABO; Theresa WEISS; Gabriel WASINGER; Torben REDMER; Heidi A. NEUBAUER; Martin SUSANI; Clemens P. SPIELVOGEL; Jing NING; Maik DAHLHOFF; Martin SCHEPELMANN; Richard KENNEDY; Richard MORIGGL; Geoffrey BROWN; Jenny PERSSON; Christopher GERNER; Vojtěch BYSTRÝ; Oldamur HOLLOCZKI; David M. HEERY; Patrick T. GUNNING; Olaf MERKEL; Brigitte HANTUSCH a Lukas KENNER. Thyroid hormone receptor beta signaling is a targetable driver of prostate cancer growth. Molecular Cancer. LONDON: BioMed Central, 2025, roč. 24, č. 1, s. 1-21. ISSN 1476-4598. Dostupné z: https://doi.org/10.1186/s12943-025-02451-2.

@article{2552019,
   author = {Fesiuk, Aleksandra and Poloske, Daniel and de Araujo, Elvin D. and Frere, Geordon A. and Wright, Timothy B. and Tin, Gary and Raouf, Yasir S. and Olaoye, Olasunkanmi O. and Park, Ji Sung and Blavet, Nicolas and Tichý, Boris and Schlederer, Michaela and Hogler, Sandra and Wolf, Michael and Philippe, Cecile and Aksoy, Osman and Varady, Adam and Medaglia Mata, Alejandro Antonio and Varenicja, Maxim and Szabo, Boglarka and Weiss, Theresa and Wasinger, Gabriel and Redmer, Torben and Neubauer, Heidi A. and Susani, Martin and Spielvogel, Clemens P. and Ning, Jing and Dahlhoff, Maik and Schepelmann, Martin and Kennedy, Richard and Moriggl, Richard and Brown, Geoffrey and Persson, Jenny and Gerner, Christopher and Bystrý, Vojtěch and Holloczki, Oldamur and Heery, David M. and Gunning, Patrick T. and Merkel, Olaf and Hantusch, Brigitte and Kenner, Lukas},
   article_location = {LONDON},
   article_number = {1},
   doi = {https://doi.org/10.1186/s12943-025-02451-2},
   keywords = {Thyroid hormone receptor beta; Prostate cancer; NH-3; Androgen receptor; Murine PCa model},
   language = {eng},
   issn = {1476-4598},
   journal = {Molecular Cancer},
   title = {Thyroid hormone receptor beta signaling is a targetable driver of prostate cancer growth},
   url = {https://link.springer.com/article/10.1186/s12943-025-02451-2?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=clarivate},
   volume = {24},
   year = {2025}
}

TY  - JOUR
ID  - 2552019
AU  - Fesiuk, Aleksandra - Poloske, Daniel - de Araujo, Elvin D. - Frere, Geordon A. - Wright, Timothy B. - Tin, Gary - Raouf, Yasir S. - Olaoye, Olasunkanmi O. - Park, Ji Sung - Blavet, Nicolas - Tichý, Boris - Schlederer, Michaela - Hogler, Sandra - Wolf, Michael - Philippe, Cecile - Aksoy, Osman - Varady, Adam - Medaglia Mata, Alejandro Antonio - Varenicja, Maxim - Szabo, Boglarka - Weiss, Theresa - Wasinger, Gabriel - Redmer, Torben - Neubauer, Heidi A. - Susani, Martin - Spielvogel, Clemens P. - Ning, Jing - Dahlhoff, Maik - Schepelmann, Martin - Kennedy, Richard - Moriggl, Richard - Brown, Geoffrey - Persson, Jenny - Gerner, Christopher - Bystrý, Vojtěch - Holloczki, Oldamur - Heery, David M. - Gunning, Patrick T. - Merkel, Olaf - Hantusch, Brigitte - Kenner, Lukas
PY  - 2025
TI  - Thyroid hormone receptor beta signaling is a targetable driver of prostate cancer growth
JF  - Molecular Cancer
VL  - 24
IS  - 1
SP  - 1-21
EP  - 1-21
PB  - BioMed Central
SN  - 14764598
KW  - Thyroid hormone receptor beta
KW  - Prostate cancer
KW  - NH-3
KW  - Androgen receptor
KW  - Murine PCa model
UR  - https://link.springer.com/article/10.1186/s12943-025-02451-2?utm_source=getftr&utm_medium=getftr&utm_campaign=getftr_pilot&getft_integrator=clarivate
N2  - 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.
ER  -

FESIUK, Aleksandra; Daniel POLOSKE; Elvin D. DE ARAUJO; Geordon A. FRERE; Timothy B. WRIGHT; Gary TIN; Yasir S. RAOUF; Olasunkanmi O. OLAOYE; Ji Sung PARK; Nicolas BLAVET; Boris TICHÝ; Michaela SCHLEDERER; Sandra HOGLER; Michael WOLF; Cecile PHILIPPE; Osman AKSOY; Adam VARADY; Alejandro Antonio MEDAGLIA MATA; Maxim VARENICJA; Boglarka SZABO; Theresa WEISS; Gabriel WASINGER; Torben REDMER; Heidi A. NEUBAUER; Martin SUSANI; Clemens P. SPIELVOGEL; Jing NING; Maik DAHLHOFF; Martin SCHEPELMANN; Richard KENNEDY; Richard MORIGGL; Geoffrey BROWN; Jenny PERSSON; Christopher GERNER; Vojtěch BYSTRÝ; Oldamur HOLLOCZKI; David M. HEERY; Patrick T. GUNNING; Olaf MERKEL; Brigitte HANTUSCH a Lukas KENNER. Thyroid hormone receptor beta signaling is a targetable driver of prostate cancer growth. \textit{Molecular Cancer}. LONDON: BioMed Central, 2025, roč.~24, č.~1, s.~1-21. ISSN~1476-4598. Dostupné z: https://doi.org/10.1186/s12943-025-02451-2.

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