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EGFR Transactivation is Regulated by Neurotensin Receptors in Cancer

Moody TW

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) which regulates the proliferation of cancer cells especially non-small cell lung cancer (NSCLC). NSCLC growth is inhibited by EGFR tyrosine kinase inhibitors (TKI) such as erlotinib or gefitinib. Gefitinib is used to treat NSCLC patients who have EGFR mutations. EGFR tyrosine phosphorylation is regulated by G protein-coupled receptors (GPCR) such as the neurotensin (NTS) receptor. EGFR transactivation caused by NTS addition to NSCLC cells is inhibited by SR48692 (NTSR1 antagonist) or gefitinib. SR48692 and gefitinib are synergistic at inhibiting NSCLC proliferation. The results indicate that GPCR antagonists can potentiate the effects of TKI in cancer.