Thyroid and androgen receptor signaling are antagonized by μ-Crystallin in prostate cancer.
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 μ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) 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.
['Aksoy|Osman|O|0000-0002-3068-455X', 'Pencik|Jan|J|', 'Hartenbach|Markus|M|', 'Moazzami|Ali A|AA|', 'Schlederer|Michaela|M|', 'Balber|Theresa|T|', 'Varady|Adam|A|', 'Philippe|Cecile|C|', 'Baltzer|Pascal A|PA|', 'Mazumder|Bismoy|B|', 'Whitchurch|Jonathan B|JB|', 'Roberts|Christopher J|CJ|', 'Haitel|Andrea|A|', 'Herac|Merima|M|', 'Susani|Martin|M|', 'Mitterhauser|Markus|M|', 'Marculescu|Rodrig|R|', 'Stangl-Kremser|Judith|J|', 'Hassler|Melanie R|MR|', 'Kramer|Gero|G|', 'Shariat|Shahrokh F|SF|', 'Turner|Suzanne D|SD|', 'Tichy|Boris|B|', 'Oppelt|Jan|J|', 'Pospisilova|Sarka|S|', 'Hartenbach|Sabrina|S|', 'Tangermann|Simone|S|', 'Egger|Gerda|G|', 'Neubauer|Heidi A|HA|', 'Moriggl|Richard|R|', 'Culig|Zoran|Z|', 'Greiner|Georg|G|', 'Hoermann|Gregor|G|', 'Hacker|Marcus|M|', 'Heery|David M|DM|', 'Merkel|Olaf|O|', 'Kenner|Lukas|L|']
D045744:Cell Line, Tumor D002794:Choline D015331:Cohort Studies D003459:Crystallins D015536:Down-Regulation D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D055432:Metabolomics D009367:Neoplasm Staging D000078722:PC-3 Cells D000072078:Positron Emission Tomography Computed Tomography D011379:Prognosis D011471:Prostatic Neoplasms D011944:Receptors, Androgen D011988:Receptors, Thyroid Hormone D017423:Sequence Analysis, RNA D015398:Signal Transduction D046888:Tissue Array Analysis D014284:Triiodothyronine D000090803:mu-Crystallins
androgen receptor μ-Crystallin prostate cancer PSMA-PET thyroid hormone receptor