TY - JOUR
T1 - PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer
AU - Zabala-Letona, Amaia
AU - Arruabarrena-Aristorena, Amaia
AU - Fernandez-Ruiz, Sonia
AU - Viera, Cristina
AU - Carlevaris, Onintza
AU - Ercilla, Amaia
AU - Mendizabal, Isabel
AU - Martin, Teresa
AU - Macchia, Alice
AU - Camacho, Laura
AU - Pujana-Vaquerizo, Mikel
AU - Sanchez-Mosquera, Pilar
AU - Torrano, Verónica
AU - Martin-Martin, Natalia
AU - Zuniga-Garcia, Patricia
AU - Castillo-Martin, Mireia
AU - Ugalde-Olano, Aitziber
AU - Loizaga-Iriarte, Ana
AU - Unda, Miguel
AU - Mato, Jose M.
AU - Berra, Edurne
AU - Martinez-Chantar, Maria L.
AU - Carracedo, Arkaitz
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Glycine N-Methyltransferase (GNMT) is a metabolic enzyme that integrates metabolism and epigenetic regulation. The product of GNMT, sarcosine, has been proposed as a prostate cancer biomarker. This enzyme is predominantly expressed in the liver, brain, pancreas, and prostate tissue, where it exhibits distinct regulation. Whereas genetic alterations in GNMT have been associated to prostate cancer risk, its causal contribution to the development of this disease is limited to cell line-based studies and correlative human analyses. Here we integrate human studies, genetic mouse modeling, and cellular systems to characterize the regulation and function of GNMT in prostate cancer. We report that this enzyme is repressed upon activation of the oncogenic Phosphoinositide-3-kinase (PI3K) pathway, which adds complexity to its reported dependency on androgen signaling. Importantly, we demonstrate that expression of GNMT is required for the onset of invasive prostate cancer in a genetic mouse model. Altogether, our results provide further support of the heavy oncogenic signal-dependent regulation of GNMT in prostate cancer.
AB - Glycine N-Methyltransferase (GNMT) is a metabolic enzyme that integrates metabolism and epigenetic regulation. The product of GNMT, sarcosine, has been proposed as a prostate cancer biomarker. This enzyme is predominantly expressed in the liver, brain, pancreas, and prostate tissue, where it exhibits distinct regulation. Whereas genetic alterations in GNMT have been associated to prostate cancer risk, its causal contribution to the development of this disease is limited to cell line-based studies and correlative human analyses. Here we integrate human studies, genetic mouse modeling, and cellular systems to characterize the regulation and function of GNMT in prostate cancer. We report that this enzyme is repressed upon activation of the oncogenic Phosphoinositide-3-kinase (PI3K) pathway, which adds complexity to its reported dependency on androgen signaling. Importantly, we demonstrate that expression of GNMT is required for the onset of invasive prostate cancer in a genetic mouse model. Altogether, our results provide further support of the heavy oncogenic signal-dependent regulation of GNMT in prostate cancer.
UR - http://www.scopus.com/inward/record.url?scp=85125438437&partnerID=8YFLogxK
U2 - 10.1038/s41389-022-00382-x
DO - 10.1038/s41389-022-00382-x
M3 - Article
AN - SCOPUS:85125438437
SN - 2157-9024
VL - 11
JO - Oncogenesis
JF - Oncogenesis
IS - 1
M1 - 10
ER -