| Item type: | Article | ||||||||||||||||||||||||||||||||||
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| Journal or Publication Title: | European journal of cancer | ||||||||||||||||||||||||||||||||||
| Publisher: | Elsevier | ||||||||||||||||||||||||||||||||||
| Volume: | 49 | ||||||||||||||||||||||||||||||||||
| Number of Issue or Book Chapter: | 6 | ||||||||||||||||||||||||||||||||||
| Page Range: | pp. 1305-1313 | ||||||||||||||||||||||||||||||||||
| Date: | April 2013 | ||||||||||||||||||||||||||||||||||
| Institutions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Pathologie | ||||||||||||||||||||||||||||||||||
| Identification Number: |
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| Classification: |
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| Keywords: | PRMT; Methylthioadenosine; Melanoma; MAPK/ERK signalling; Protein arginine methylation | ||||||||||||||||||||||||||||||||||
| Dewey Decimal Classification: | 500 Science > 500 Natural sciences & mathematics 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||||
| Refereed: | Yes, this version has been refereed | ||||||||||||||||||||||||||||||||||
| Created at the University of Regensburg: | Partially | ||||||||||||||||||||||||||||||||||
| Item ID: | 30573 |
Abstract
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. ...
Abstract
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.
Metadata last modified: 25 May 2018 13:15
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