G Protein-coupled Receptors As Oncogenic Signals in Glioma: Emerging Therapeutic Avenues

Overview

Journal Neuroscience

Specialty Neurology

Date 2014 Aug 28

PMID 25158675

Citations 23

Authors

A E Cherry

N Stella

Affiliations

Soon will be listed here.

Abstract

Gliomas are the most common malignant intracranial tumors. Newly developed targeted therapies for these cancers aim to inhibit oncogenic signals, many of which emanate from receptor tyrosine kinases, including the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR). Unfortunately, the first-generation treatments targeting these oncogenic signals provide little survival benefit in both mouse xenograft models and human patients. The search for new treatment options has uncovered several G protein-coupled receptor (GPCR) candidates and generated a growing interest in this class of proteins as alternative therapeutic targets for the treatment of various cancers, including glioblastoma multiforme (GBM). GPCRs constitute a large family of membrane receptors that influence oncogenic pathways through canonical and non-canonical signaling. Accordingly, evidence indicates that GPCRs display a unique ability to crosstalk with receptor tyrosine kinases, making them important molecular components controlling tumorigenesis. This review summarizes the current research on GPCR functionality in gliomas and explores the potential of modulating these receptors to treat this devastating disease.

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References

Blazquez C, Galve-Roperh I, Guzman M . De novo-synthesized ceramide signals apoptosis in astrocytes via extracellular signal-regulated kinase. FASEB J. 2000; 14(14):2315-22. DOI: 10.1096/fj.00-0122com. View

Bao S, Wu Q, McLendon R, Hao Y, Shi Q, Hjelmeland A . Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006; 444(7120):756-60. DOI: 10.1038/nature05236. View

Yoshida Y, Nakada M, Harada T, Tanaka S, Furuta T, Hayashi Y . The expression level of sphingosine-1-phosphate receptor type 1 is related to MIB-1 labeling index and predicts survival of glioblastoma patients. J Neurooncol. 2009; 98(1):41-7. DOI: 10.1007/s11060-009-0064-5. View

Wong A, Bigner S, Bigner D, Kinzler K, Hamilton S, Vogelstein B . Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci U S A. 1987; 84(19):6899-903. PMC: 299192. DOI: 10.1073/pnas.84.19.6899. View

Ceradini D, Kulkarni A, Callaghan M, Tepper O, Bastidas N, Kleinman M . Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004; 10(8):858-64. DOI: 10.1038/nm1075. View

SUGAWA N, Ekstrand A, James C, Collins V . Identical splicing of aberrant epidermal growth factor receptor transcripts from amplified rearranged genes in human glioblastomas. Proc Natl Acad Sci U S A. 1990; 87(21):8602-6. PMC: 55005. DOI: 10.1073/pnas.87.21.8602. View

Sanchez C, Galve-Roperh I, Canova C, Brachet P, Guzman M . Delta9-tetrahydrocannabinol induces apoptosis in C6 glioma cells. FEBS Lett. 1998; 436(1):6-10. DOI: 10.1016/s0014-5793(98)01085-0. View

Balthasar S, Samulin J, Ahlgren H, Bergelin N, Lundqvist M, Toescu E . Sphingosine 1-phosphate receptor expression profile and regulation of migration in human thyroid cancer cells. Biochem J. 2006; 398(3):547-56. PMC: 1559461. DOI: 10.1042/BJ20060299. View

Friedman H, Prados M, Wen P, Mikkelsen T, Schiff D, Abrey L . Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009; 27(28):4733-40. DOI: 10.1200/JCO.2008.19.8721. View

10.

Schafer B, Marg B, Gschwind A, Ullrich A . Distinct ADAM metalloproteinases regulate G protein-coupled receptor-induced cell proliferation and survival. J Biol Chem. 2004; 279(46):47929-38. DOI: 10.1074/jbc.M400129200. View

11.

Chen J, Bian X, Yao X, Gong W, Hu J, Chen K . Nordy, a synthetic lipoxygenase inhibitor, inhibits the expression of formylpeptide receptor and induces differentiation of malignant glioma cells. Biochem Biophys Res Commun. 2006; 342(4):1368-74. DOI: 10.1016/j.bbrc.2006.02.113. View

12.

Stevenson C, Ehtesham M, McMillan K, Valadez J, Edgeworth M, Price R . CXCR4 expression is elevated in glioblastoma multiforme and correlates with an increase in intensity and extent of peritumoral T2-weighted magnetic resonance imaging signal abnormalities. Neurosurgery. 2008; 63(3):560-9. PMC: 2602832. DOI: 10.1227/01.NEU.0000324896.26088.EF. View

13.

Libermann T, Nusbaum H, Razon N, Kris R, Lax I, Soreq H . Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985; 313(5998):144-7. DOI: 10.1038/313144a0. View

14.

Hart S, Fischer O, Prenzel N, Zwick-Wallasch E, Schneider M, Hennighausen L . GPCR-induced migration of breast carcinoma cells depends on both EGFR signal transactivation and EGFR-independent pathways. Biol Chem. 2005; 386(9):845-55. DOI: 10.1515/BC.2005.099. View

15.

Thomas S, Bhola N, Zhang Q, Contrucci S, Wentzel A, Freilino M . Cross-talk between G protein-coupled receptor and epidermal growth factor receptor signaling pathways contributes to growth and invasion of head and neck squamous cell carcinoma. Cancer Res. 2006; 66(24):11831-9. DOI: 10.1158/0008-5472.CAN-06-2876. View

16.

Richard D, Vouret-Craviari V, Pouyssegur J . Angiogenesis and G-protein-coupled receptors: signals that bridge the gap. Oncogene. 2001; 20(13):1556-62. DOI: 10.1038/sj.onc.1204193. View

17.

Piiper A, Zeuzem S . Receptor tyrosine kinases are signaling intermediates of G protein-coupled receptors. Curr Pharm Des. 2004; 10(28):3539-45. DOI: 10.2174/1381612043382936. View

18.

Filardo E, Quinn J, Bland K, Frackelton Jr A . Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol Endocrinol. 2000; 14(10):1649-60. DOI: 10.1210/mend.14.10.0532. View

19.

Sun R, Iribarren P, Zhang N, Zhou Y, Gong W, Cho E . Identification of neutrophil granule protein cathepsin G as a novel chemotactic agonist for the G protein-coupled formyl peptide receptor. J Immunol. 2004; 173(1):428-36. DOI: 10.4049/jimmunol.173.1.428. View

20.

Pierce K, Premont R, Lefkowitz R . Seven-transmembrane receptors. Nat Rev Mol Cell Biol. 2002; 3(9):639-50. DOI: 10.1038/nrm908. View