Acta Scientific Pharmaceutical Sciences (ASPS)(ISSN: 2581-5423)

Review Article Volume 8 Issue 2

G Protein-Coupled Receptors (GPCRs) Mediated Signaling Pathway, An Essential Drug Targets in Tumor Regulation: An Overview

Muhammad Mehran Mouzam*, Aamna Bibi, Noman Haider Khan, Watiba Danish, Fatima Naveed and Ayiza Sulaiman

Faculty of Veterinary Science, University of Agriculture Faisalabad, Pakistan

*Corresponding Author: Muhammad Mehran Mouzam, Faculty of Veterinary Science, University of Agriculture Faisalabad, Pakistan.

Received: September 01, 2023; Published: December 24, 2023

Abstract

G protein-coupled receptors (GPCRs) are the integral membrane proteins used by the cell to convert the extracellular signals into intracellular responses. The GPCR stimulates signaling mediated by β-arrestins or G protein to exert forces of movement during metastasis and tumor cell. The GPCR mediated ERK/MAPK activation triggers multiple pathways that can regulate crosstalk between GPCR and receptor tyrosine kinase (RTK) signaling, which is responsible to many cellular functions with activated MAPK cascades. The components of ERK signaling cascade are attractive targets for drug development. ERK signaling cascade also enhanced inhibition of ERK signaling in the tumor, which is required for effective treatment of RAS/RAF mutant cancers. However, when ERK is activated, ERK is transported to the nucleus, and promotes a transcription of mitogenesis and proliferation related target genes. The activation of ERK via cytokines initiate expression level of transcription factors, protein kinase and regulatory genes, which is capable of regulating cell migration, differentiation, survival, proliferation, and apoptosis with rapidness and sequence. Furthermore, Wnt/β-catenin signaling pathway can regulate tumor progression via Wnt ligand interaction by promoting metastatic growth and resistance to chemotherapy in breast cancer. In this review, the significance of different GPCRs mediated signaling pathways capable of regulating cellular migration, differentiation, apoptosis, proliferation, cell survival, and tumor progression which helps to treat tumor cell.

Keywords: Cancer Progression; GPCR; Cytokines/ERK1/2 Signaling; GRK/β-arrestin Signaling; Wnt/ β-catenin Pathway; MAPK Pathway

References

  1. Dwivedi H., et al. “GPCR Signaling: The Interplay of Gαi and β-arrestin”. Current Biology: CB7 (2018): R324-R327.
  2. Zhao J., et al. “G Protein-Coupled Receptors (GPCRs) in Alzheimer's Disease: A Focus on BACE1 Related GPCRs”. Frontiers in Aging Neuroscience 8 (2016): 58.
  3. Bianca P., et al. “Emerging Role of Compartmentalized G Protein-Coupled Receptor Signaling in the Cardiovascular Field”. ACS Pharmacology and Translational Science2 (2020): 221-236.
  4. Gougeon RD. “Chemical messages from an ancient buried bottle: metabolomics for wine archeochemistry”. npjence of Food1 (2017): 1.
  5. Grushevskyi EO., et al. “Stepwise activation of a class C GPCR begins with millisecond dimer rearrangement”. Proceedings of the National Academy of Sciences20 (2019): 10150-10155.
  6. Van G., et al. “β-Arrestin Based Receptor Signaling Paradigms: Potential Therapeutic Targets for Complex Age-Related Disorders”. Frontiers in Pharmacology 9 (2018).
  7. Liu Y., et al. “G protein-coupled receptors as promising cancer targets”. Cancer Letters2 (2016): 226-239.
  8. Gutierrez AN and PH McDonald. “GPCRs: Emerging anti-cancer drug targets”. Cellular Signalling, 41 (2018): 65-74.
  9. Eichel K and MV Zastrow. “Subcellular Organization of GPCR Signaling”. Trends in Pharmacological Sciences2 (2018): 200-208.
  10. Hauser AS., et al. “Pharmacogenomics of GPCR drug targets”. Cell1-2 (2018): 41-54. e19.
  11. Jacobson KA. “New paradigms in GPCR drug discovery”. Current Topics in Medicinal Chemistry4 (2015): 541-555.
  12. Yu S., et al. “The role of G protein-coupled receptor kinases in cancer”. International Journal of Biological Sciences2 (2018): 189.
  13. Nogués L., et al. “G protein-coupled receptor kinases (GRKs) in tumorigenesis and cancer progression: GPCR regulators and signaling hubs”. in Seminars in cancer biology. Elsevier (2018).
  14. Nogués L., et al. “G-Protein-Coupled Receptor Kinase 2 as a Potential Modulator of the Hallmarks of Cancer”. Molecular Pharmacology3 (2017): 220-228.
  15. Sun WY., et al. “Down-regulation of β-arrestin2 promotes tumour invasion and indicates poor prognosis of hepatocellular carcinoma”. Scientific Reports 6 (2016): 35609.
  16. Quốc Lu'o'ng KV and LT Nguyễn. “The roles of beta-adrenergic receptors in tumorigenesis and the possible use of beta-adrenergic blockers for cancer treatment: possible genetic and cell-signaling mechanisms”. Cancer Management and Research (2012): 431-445.
  17. Kitanaka N., et al. “Interleukin-1β promotes interleulin-6 expression via ERK1/2 signaling pathway in canine dermal fibroblasts”. PloS One7 (2019).
  18. Xu D., et al. “TPL2 kinase action and control of inflammation”. Pharmacological Research 129 (2018): 188-193.
  19. , et al. “The MAPK Signaling Pathways as a Novel Way in Regulation and Treatment of Parasitic Diseases”. Diseases (2019).
  20. Sun Y., et al. “Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis”. Journal of Receptor and Signal Transduction Research6 (2015): 1-5.
  21. Olea-Flores M., et al. “Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition in Cancer”. International Journal of Molecular Sciences12 (2017): 2885.
  22. Zhang N and PE Kima. “Leishmania infection engages non-receptor protein kinases differentially to persist in infected hosts”. Frontiers in Immunology 7 (2019): 146.
  23. Sun J and G Nan. “The extracellular signal-regulated kinase 1/2 pathway in neurological diseases: A potential therapeutic target (Review)”. International Journal of Molecular Medicine6 (2017): 1338-1346.
  24. Samatar AA and PI Poulikakos. “Targeting RAS-ERK signalling in cancer: promises and challenges”. Nature Reviews Drug Discovery12 (2014): 928-942.
  25. Du Z and CM Lovly. “Mechanisms of receptor tyrosine kinase activation in cancer”. Molecular Cancer1 (2018): 58.
  26. de Souza AP., et al. “MAPK involvement in cytokine production in response to Corynebacterium pseudotuberculosis infection”. BMC Microbiology1 (2014): 230.
  27. Lee M and I Rhee. “Cytokine signaling in tumor progression”. Immune Network4 (2018): 214-227.
  28. Zundler S and MF Neurath. “Integrating immunologic signaling networks: the JAK/STAT pathway in colitis and colitis-associated cancer”. Vaccines1 (2016): 5.
  29. Cai B., et al. “The specific roles of JAK/STAT signaling pathway in sepsis”. Inflammation4 (2015): 1599-1608.
  30. Liu Y., et al. “Opportunities for translation from the bench: therapeutic intervention of the JAK/STAT pathway in neuroinflammatory diseases”. Critical Reviews™ in Immunology6 (2015).
  31. Lee MJ. “Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance”. Genes and Diseases1 (2016): 11-40.
  32. Tang X., et al. “Roles of N-glycosylation and lipidation in Wg secretion and signaling”. Developmental Biology 1 (2012): 32-41.
  33. Nusse R and H Clevers. “Wnt/β-catenin signaling, disease, and emerging therapeutic modalities”. Cell 6 (2017): 985-999.
  34. Haseeb M., et al. “Wnt Signaling in the Regulation of Immune Cell and Cancer Therapeutics”. Cells 11 (2019): 1380.
  35. Nakajima EC and B Van Houten. “Metabolic symbiosis in cancer: refocusing the Warburg lens”. Molecular Carcinogenesis 5 (2013): 329-337.
  36. Martin-Orozco E., et al. “WNT signaling in tumors: the way to evade drugs and immunity”. Frontiers in Immunology 10 (2019).
  37. Polakis P. “Wnt signaling in cancer”. Cold Spring Harbor Perspectives in Biology5 (2022): a008052.
  38. Li S., et al. “The expression of β-catenin in different subtypes of breast cancer and its clinical significance”. Tumor Biology8 (2014): 7693-7698.
  39. Cui J., et al. “Role of Wnt/β-catenin signaling in drug resistance of pancreatic cancer”. Current Pharmaceutical Design 17 (2012): 2464-2471.
  40. Sherwood V. “WNT signaling: an emerging mediator of cancer cell metabolism?” Molecular and Cellular Biology 1 (2015): 2-10.
  41. Duchartre Y., et al. “The Wnt signaling pathway in cancer”. Critical Reviews in Oncology/Hematology 99 (2016): 141-149.
  42. Davey CF and CB Moens. “Planar cell polarity in moving cells: think globally, act locally”. Development2 (2017): 187-200.
  43. Davey CF., et al. “PCP signaling between migrating neurons and their planar-polarized neuroepithelial environment controls filopodial dynamics and directional migration”. PLoS Genetics3 (2016).

Citation

Citation: Muhammad Mehran Mouzam., et al. “G Protein-Coupled Receptors (GPCRs) Mediated Signaling Pathway, An Essential Drug Targets in Tumor Regulation: An Overview".Acta Scientific Pharmaceutical Sciences 8.1 (2024): 85-93.

Copyright

Copyright: © 2024 Muhammad Mehran Mouzam., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.




Metrics

Acceptance rate32%
Acceptance to publication20-30 days

Indexed In




News and Events


  • Certification for Review
    Acta Scientific certifies the Editors/reviewers for their review done towards the assigned articles of the respective journals.
  • Submission Timeline for Upcoming Issue
    The last date for submission of articles for regular Issues is April 30th, 2024.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of "Best Article of the Issue".
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.

Contact US