黑色素瘤
甲基化
间质细胞
癌症研究
MAPK/ERK通路
甲基转移酶
激酶
生物
细胞生物学
生物化学
基因
作者
Katharina Limm,Corinna Ott,Susanne Wallner,Daniel Mueller,Peter J. Oefner,Claus Hellerbrand,Anja‐Katrin Bosserhoff
标识
DOI:10.1016/j.ejca.2012.11.026
摘要
Loss of methylthioadenosine phosphorylase (MTAP) expression and a concomitant accumulation of 5′-methyl-thioadenosine (MTA) characterise several tumour entities including malignant melanoma. MTA affects cellular signalling, proliferation and migration not only of cancer but also surrounding cells including lymphocytes and stromal fibroblasts. The mode of action of MTA is still not known. Interestingly, MTA is a known potent inhibitor of protein arginine methyltransferases (PRMTs) and is used as a tool in studying activity and impact of PRMTs. This study aimed at analysing PRMTs in melanoma and the potential impact of MTA on tumourigenesis. Our findings demonstrate that expression of PRMT4/CARM1 and PRMT6 is deregulated in melanoma, whereas expression of the remaining PRMTs stays unchanged. General PRMT activity and, consequently, symmetric and asymmetric protein methylation are reduced significantly in melanoma cells and tissues. This is due to a loss of MTAP expression and accumulation of MTA. Reduction of protein methylation by MTA affects cell signalling and leads, for example, to an activation of extracellular signal-regulated kinase (ERK) activity. The effects of endogeneous MTA on PRMTs as presented in this study can strongly support the migratory and invasive phenotype of melanoma cells.
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