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@article{1603680,
author = {Strmiska, Vladislav and Michalek, Petr and Lackova, Zuzana and Guran, Roman and Krizkova, Sona and Vanickova, Lucie and Zitka, Ondrej and Stiborova, Marie and Eckschlager, Tomas and Klejdus, Borivoj and Pacík, Dalibor and Tvrdikova, Eliska and Keil, Claudia and Haase, Hajo and Adam, Vojtech and Heger, Zbynek},
article_location = {Oxford},
article_number = {5},
doi = {http://dx.doi.org/10.1002/1878-0261.12439},
keywords = {DNA methylation; Dnmts; epigenetics; prostate cancer; SAMe; sarcosine},
language = {eng},
issn = {1574-7891},
journal = {Molecular oncology},
title = {Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axis},
url = {http://dx.doi.org/10.1002/1878-0261.12439},
volume = {13},
year = {2019}
}
TY - JOUR
ID - 1603680
AU - Strmiska, Vladislav - Michalek, Petr - Lackova, Zuzana - Guran, Roman - Krizkova, Sona - Vanickova, Lucie - Zitka, Ondrej - Stiborova, Marie - Eckschlager, Tomas - Klejdus, Borivoj - Pacík, Dalibor - Tvrdikova, Eliska - Keil, Claudia - Haase, Hajo - Adam, Vojtech - Heger, Zbynek
PY - 2019
TI - Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axis
JF - Molecular oncology
VL - 13
IS - 5
SP - 1002-1017
EP - 1002-1017
PB - Elsevier Science Inc.
SN - 15747891
KW - DNA methylation
KW - Dnmts
KW - epigenetics
KW - prostate cancer
KW - SAMe
KW - sarcosine
UR - http://dx.doi.org/10.1002/1878-0261.12439
L2 - http://dx.doi.org/10.1002/1878-0261.12439
N2 - DNA hypermethylation is one of the most common epigenetic modifications in prostate cancer (PCa). Several studies have delineated sarcosine as a PCa oncometabolite that increases the migration of malignant prostate cells while decreasing their doubling time. Here, we show that incubation of prostate cells with sarcosine elicited the upregulation of sarcosine N-demethylation enzymes, sarcosine dehydrogenase and pipecolic acid oxidase. This process was accompanied by a considerable increase in the production of the major methyl-donor S-adenosylmethionine (SAMe), together with an elevation of cellular methylation potential. Global DNA methylation analyses revealed increases in methylated CpG islands in distinct prostate cell lines incubated with sarcosine, but not in cells of nonprostate origin. This phenomenon was further associated with marked upregulation of DNA methyltransferases (Dnmts). Epigenetic changes were recapitulated through blunting of Dnmts using the hypomethylating agent 5-azacytidine, which was able to inhibit sarcosine- induced migration of prostate cells. Moreover, spatial mapping revealed concomitant increases in sarcosine, SAMe and Dnmt1 in histologically confirmed malignant prostate tissue, but not in adjacent or nonmalignant tissue, which is in line with the obtained in vitro data. In summary, we show here for the first time that sarcosine acts as an epigenetic modifier of prostate cells and that this may contribute to its oncometabolic role.
ER -
STRMISKA, Vladislav, Petr MICHALEK, Zuzana LACKOVA, Roman GURAN, Sona KRIZKOVA, Lucie VANICKOVA, Ondrej ZITKA, Marie STIBOROVA, Tomas ECKSCHLAGER, Borivoj KLEJDUS, Dalibor PACÍK, Eliska TVRDIKOVA, Claudia KEIL, Hajo HAASE, Vojtech ADAM and Zbynek HEGER. Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axis. \textit{Molecular oncology}. Oxford: Elsevier Science Inc., 2019, vol.~13, No~5, p.~1002-1017. ISSN~1574-7891. Available from: https://dx.doi.org/10.1002/1878-0261.12439.
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