Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 148, Issue 3, Pages 731-747Publisher
WILEY
DOI: 10.1002/ijc.33332
Keywords
μ ‐ Crystallin; androgen receptor; prostate cancer; PSMA‐ PET; thyroid hormone receptor
Categories
Funding
- Siemens
- MEYS CR [LQ1601, LM22018132]
- Max Kade fellowship of the Austrian Academy of Sciences
- University of Nottingham
- University of Nottingham Vice Chancellors award
- Austrian Science Fund (FWF) [SFB-F06105, SFB-F04707, P26011, P23579-B]
- BBSRC Doctoral Training program [BB/M008770/1]
- Margaretha Hehberger Stiftung [15142]
- BM Fonds [15142]
- National Foundation for Research, Technology and Development
- Austrian Federal Ministry for Transport, Innovation and Technology
- Christian Doppler Laboratory for Applied Metabolomics (CDL-AM)
- COMET Competence Center CBmed-Center for Biomarker Research in Medicine [FA791A0906.FFG]
- Jubilaumsfond der Osterreichischen Nationalbank [14856]
- EckertAMP
- Ziegler Radiopharma
- Liechtenstein
- Austrian Science Fund (FWF) [P26011] Funding Source: Austrian Science Fund (FWF)
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Thyroid hormone, particularly through the action of CRYM, plays a role in the progression of PCa and may be involved in its recurrence. CRYM also affects choline uptake in PCa patients and is associated with imaging results.
Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3 '-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein mu-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TR alpha/TR beta) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.
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