Thyroid and androgen receptor signaling are antagonized by mu-Crystallin in prostate cancer

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Authors

AKSOY O. PENCIK J. HARTENBACH M. MOAZZAMI A.A. SCHLEDERER M. BALBER T. VARADY A. PHILIPPE C. BALTZER P.A. MAZUMDER B. WHITCHURCH J.B. ROBERTS C.J. HAITEL A. HERAC M. SUSANI M. MITTERHAUSER M. MARCULESCU R. STANGL-KREMSER J. HASSLER M.R. KRAMER G. SHARIAT S.F. TURNER Suzanne Dawn TICHÝ Boris OPPELT Jan POSPÍŠILOVÁ Šárka HARTENBACH S. TANGERMANN S. EGGER G. NEUBAUER H.A. MORIGGL R. CULIG Z. GREINER G. HOERMANN G. HACKER M. HEERY D.M. MERKEL O. KENNER L.

Year of publication 2021
Type Article in Periodical
Magazine / Source International journal of cancer
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://onlinelibrary.wiley.com/doi/10.1002/ijc.33332
Doi http://dx.doi.org/10.1002/ijc.33332
Keywords µ - Crystallin; androgen receptor; prostate cancer; PSMA- PET; thyroid hormone receptor
Description 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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