Abstract
G protein-coupled receptors (GPCRs) play a central role in signal transmission, thereby controlling many facets of cellular function. Overwhelming evidence now implicates GPCRs, G proteins and their downstream signaling targets in cancer initiation and progression, where they can influence aberrant cell growth and survival, largely through activation of AKT/mTOR, MAPKs, and Hippo signaling pathways. GPCRs also play critical roles in the invasion and metastasis of cancer cells via activation of Rho GTPases and cytoskeletal changes, and angiogenesis to supply the tumor with nutrients and provide routes for metastasis. Lastly, GPCRs contribute to the establishment and maintenance of a permissive tumor microenvironment. Understanding GPCR involvement in cancer malignancy may help identify novel therapeutic opportunities for cancer prevention and treatment.
Published by Elsevier Ltd.
Publication types
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Research Support, N.I.H., Intramural
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Review
MeSH terms
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Animals
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Cell Proliferation
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Cell Survival
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Cytoskeleton / metabolism
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GTP-Binding Proteins / genetics
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GTP-Binding Proteins / metabolism*
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Humans
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MAP Kinase Signaling System
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Neoplasms / blood supply
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Neoplasms / genetics
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Neoplasms / metabolism*
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Neoplasms / pathology
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Neovascularization, Pathologic
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Phosphatidylinositol 3-Kinases / metabolism
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Proto-Oncogene Proteins c-akt / metabolism
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Receptor Cross-Talk
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism*
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Second Messenger Systems
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Signal Transduction*
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TOR Serine-Threonine Kinases / metabolism
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Tumor Suppressor Proteins / metabolism
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Viral Proteins / metabolism
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rho GTP-Binding Proteins / metabolism
Substances
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Receptors, G-Protein-Coupled
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Tumor Suppressor Proteins
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Viral Proteins
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases
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GTP-Binding Proteins
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rho GTP-Binding Proteins