Correction added after online publication February 2012: The figure citations were incorrect in the previous version. Figure 1 has been changed to Figure 2 and vice-versa.
Glutamatergic signaling in cellular transformation
Article first published online: 20 FEB 2012
© 2012 John Wiley & Sons A/S
Pigment Cell & Melanoma Research
Volume 25, Issue 3, pages 331–342, May 2012
How to Cite
Teh, J. L. F. and Chen, S. (2012), Glutamatergic signaling in cellular transformation. Pigment Cell & Melanoma Research, 25: 331–342. doi: 10.1111/j.1755-148X.2012.00983.x
- Issue published online: 17 APR 2012
- Article first published online: 20 FEB 2012
- Accepted manuscript online: 24 JAN 2012 08:14AM EST
- PUBLICATION DATA Received 20 October 2011, revised and accepted for publication 20 January 2012, published online 24 January 2012
The role of the glutamatergic system in cancer cell homeostasis has expanded exponentially over the last decade. Once thought to participate only in synaptic transmission and neuronal excitability, the presence of functional glutamate receptors has since been demonstrated in peripheral tissues. Most notable is the implication of glutamate receptors in the pathophysiology of various human malignancies. We previously described the oncogenic properties of metabotropic glutamate receptor 1 (Grm1), a G-protein-coupled receptor in melanoma development in vivo. TG-3, a transgenic mouse line, developed spontaneous melanoma with 100% penetrance in the absence of any known stimuli. Stable Grm1-mouse melanocytic clones display transformed phenotypes in vitro and were aggressively tumorigenic in vivo. Recent reports from other groups implicate two additional members of the metabotropic glutamate receptor family in melanomagenesis, overexpression of mGluR5 and activating mutations in GRM3. These findings highlight a previously underappreciated link between the glutamate signaling pathway and oncogenesis in melanoma biology, raising exciting possibilities in elucidating mechanisms in melanocyte transformation and exploring glutamate receptors as novel therapeutic targets. Here we further consider the potential mechanisms by which glutamate receptors can function as an oncogene leading to malignant transformation.