The metabolite 5′-methylthioadenosine signals through the adenosine receptor A2B in melanoma

Limm K, Wallner S, Milenkovi VM, Wetzel CH, Bosserhoff AK (2014)

Publication Type: Journal article

Publication year: 2014

Journal

European Journal of Cancer Elsevier

Book Volume: 50

Pages Range: 2714-2724

Journal Issue: 15

DOI: 10.1016/j.ejca.2014.07.005

Abstract

Several recent studies have shown evidence supporting the general knowledge that tumour cells exhibit changes in metabolism. It is becoming increasingly important to understand how these metabolic changes in tumour cells promote carcinogenesis and disease progression. We recently discovered a lack of methylthioadenosine phosphorylase (MTAP) expression in melanoma, which resulted in an accumulation of the metabolite 5′-methylthioadenosine (MTA) in melanoma cells and in the extracellular environment. MTA was shown to affect cell proliferation of surrounding stroma cells and cell invasiveness and the activation of the transcription factor activator protein-1 (AP-1) in melanoma cells. In this study, we addressed the regulation of cellular signalling by extracellular MTA accumulation. By focusing on putative receptors that could modulate MTA signalling, we identified the adenosine receptor ADORA2B as an important candidate. Knockdown experiments and the use of specific agonists and antagonists confirmed a link between MTA and AP-1 signalling through the ADORA2B receptor. Interestingly, stimulation of the cells with MTA did not result in activation of the classical cyclic adenosine monophosphate (cAMP) signalling cascades or in Ca2+-dependent signalling. We instead showed protein kinase C (PKC) signalling to be involved in MTA-mediated AP-1 activation. In summary, we identified ADORA2B to be the specific receptor and signalling pathway for the metabolite MTA. These findings may influence the use of MTA in a therapeutic manner.

Authors with CRIS profile

Anja Katrin Boßerhoff

Involved external institutions

Universität Regensburg DE Germany (DE)

How to cite

APA:

Limm, K., Wallner, S., Milenkovi, V.M., Wetzel, C.H., & Bosserhoff, A.K. (2014). The metabolite 5′-methylthioadenosine signals through the adenosine receptor A2B in melanoma. European Journal of Cancer, 50(15), 2714-2724. https://dx.doi.org/10.1016/j.ejca.2014.07.005

MLA:

Limm, Katharina, et al. "The metabolite 5′-methylthioadenosine signals through the adenosine receptor A2B in melanoma." European Journal of Cancer 50.15 (2014): 2714-2724.

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