Cross Talk Between Galanin Receptor 2 and EGFR in Oral Cancer
Smith, Alison R.
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Squamous cell carcinoma of the head and neck (SCCHN) is one of the ten most common cancers globally. Unfortunately, the survival rate for this disease is generally poor and treatment options are limited. High cellular expression of factors such as the activated epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is associated with tumor progression and poor patient survival rates in SCCHN. EGFR-targeted therapies have been marginally successful in the treatment of SCCHN, suggesting that other signaling pathways work in conjunction with EGFR to promote tumor progression. It has been shown that activation of gastrin-releasing peptide receptor, a G protein-coupled receptor, resulted in phosphorylation of EGFR in SCCHN cells (Lui et al., 2003). Importantly, we recently showed that Galanin Receptor 2 (GALR2), also a G protein-coupled receptor, promotes progression of SCCHN (Banerjee et al., 2011). These data lead us to explore the role of GALR2 in EGFR activation in SCCHN. We explored activation of EGFR (by phosphorylation at the Y1068 active site) by stimulating endogenous GALR2 with one of two GALR2-specific agonists, and by stimulating stably over expressing GALR2 cell lines with different concentrations of galanin. Western Blot analysis was used to visualize the activation of EGFR in each treatment group. We found that stimulation of endogenous as well as cells that stably over express GALR2 resulted in phosphorylation of EGFR in SCCHN cells. These results confirm the relationship between GALR2 and EGFR in SCCHN. Because we have seen that stimulation of GALR2 phosphorylates EGFR, we will investigate whether this mechanism modulates response to EGFR antagonists. This information may lead to the development of a more specific SCCHN treatment targeting both EGFR and GALR2, in order to compensate for cross talk occurring between these two receptors.