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Peptide receptors as cancer drug targets
Author(s) -
Moody Terry W.
Publication year - 2019
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.14100
Subject(s) - bombesin , g protein coupled receptor , vasoactive intestinal peptide , receptor , autocrine signalling , microbiology and biotechnology , adenylyl cyclase , mapk/erk pathway , signal transduction , paracrine signalling , neuropeptide , kinase , creb , protein kinase a , phosphorylation , biology , chemistry , biochemistry , transcription factor , gene
Neuropeptides function as neuromodulators in the brain, whereby they are released in a paracrine manner and activate G protein–coupled receptors (GPCRs) in adjacent cells. Because neuropeptides are made in, and secreted from, cancer cells, then bind to cell surface receptors, they function in an autocrine manner. Bombesin (BB)‐like peptides synthesized by neuroendocrine tumor small cell lung cancer (SCLC) bind to BB receptors (BBRs), causing phosphatidylinositol turnover and phosphorylation of extracellular signal–regulated kinase (ERK). Phosphorylated ERK enters the nucleus and alters gene expression of SCLC cells, stimulating growth. Vasoactive intestinal peptide (VIP) addition to SCLC cells increases their release rate of BB‐like peptides via activation of VIP receptors (VIPR), leading to activation of adenylyl cyclase and subsequent elevation of cAMP. Protein kinase A is then stimulated, leading to phosphorylation of cyclic AMP response element binding protein (CREB), which alters gene expression and stimulates proliferation. The growth of SCLC is inhibited by BBR and VIPR antagonists. This review will focus on how GPCRs for VIP and BB are molecular targets for early detection and treatment of cancer.