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 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.

Rudolfinerhaus
The University of Texas Medical Branch at Galveston
Sechenov University
Univ Jordan
Cornell University
Salk Inst Biol Studies
The University of Texas Southwestern Medical Center
Histo Consulting Inc
Masaryk Universität
Ludwig Boltzmann Institute Applied Diagnostics
University of Nottingham
MLL Münchner Leukämielabor GmbH
University of Cambridge
CBmed GmbH
Karls-Universität Prag
Medizinische Universität Innsbruck
Medizinische Universität Wien - AKH
Universität Wien
Veterinärmedizinische Universität Wien
Swedish University of Agricultural Sciences
Salk Institute
University of Jordan