Glutamatergic signaling in cellular transformation

Jessica L.F. Teh, Suzie Chen

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)331-342
Number of pages12
JournalPigment Cell and Melanoma Research
Issue number3
StatePublished - May 2012

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology


  • Grm1
  • MGluR1
  • Melanoma


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