Insight into the interplay between metabolism of sarcosine and calmodulin-dependent signalling in prostate cells

prezentace, poster

angličtina

Prostate cancer (PCa) is the most common solid neoplasm w orldwide. Sarcosine, an intermediate and byproduct in glycine metabolism, represents a potential urinary biomarker exploitable for early PCa diagnosis. Concentration of sarcosine is substantially increased during PCa progression to its metastasis. Sarcosine has been shown to affect several genes involved in cell cycle and apoptosis. Nevertheless the mechanism responsible for these phenomena remains unknown. Calmodulin (CaM) is a ubiquitous calcium-binding protein. It is responsible for intracellular interactions connected with regulation of proliferation and malignity. CaM acts primarily through CaM-dependent signalling pathways connected into regulatory system important for cellular pathophysiology. CaM-dependent protein kinases are activated after ihe presence of CaM in neighbouring subunits activated by Ca2* ions. If CaM is accumulated in a sufficient amount, autophosphorylation occurs, leading to persistent activation of the enzyme. The major mediator system affecting cellular proliferation driven by Ctt"'/CaM is CaM-dependent protein kinase II (CaMKII). CaMKII phosphorylates over 40 different proteins, including enzymes, kinases and transcription factors. Our results demonstrate a unique connection between sarcosine exposure and CaM expression. This results in upregulation of CaM kinases and alteration in their phosphorylation status. We also show that sarcosine affects Ca'" homeostasis. Moreover, functional siRNA analyses revealed an importance of CaM-sareosine interplay in proliferation and clonogenicity of prostate cells.

Sarcosine; calmodulin; prostate cancer

STRMISKA, V.; MICHÁLEK, P.; KŘÍŽKOVÁ, S.; GURÁŇ, R.; ZÍTKA, O.; ŠTUŘÍKOVÁ, H.; KRYŠTOFOVÁ, O.; ŠTĚRBOVÁ, D.; ADAM, V.; HEGER, Z.

1. 12. 2018

S22

S22

1