Special Issue "G-Protein Coupled Receptors in Cancer"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: closed (15 January 2022).

Special Issue Editor

Dr. Anthony Ashton
E-Mail Website
Guest Editor
Division of Cardiovascular Medicine, Lankenau Institute for Medical Research, Wynnewood, PA 19096, USA
Interests: G-protein coupled receptors; Angiogenesis; Cardiac remodeling; Pregnancy; Placentation

Special Issue Information

Dear Colleagues,

G-protein-coupled receptors (GPCRs) are the largest family of plasma membrane receptors. Signaling by heterotrimeric G-proteins begins when ligand binding to the GPCR triggers a conformational change promoting proximity of the GEF domain and the GDP-bound heterotrimeric G-protein. GTP exchange liberates the a-subunit from the bg-subunits and initiates signal transduction. G-protein inactivation occurs when GTP hydrolyses to GDP in the a-subunit (promoted by RGS proteins) and the bg-subunits re-associate. The pathway may also be inhibited by phosphorylation of the GPCR by protein kinases, the subsequent binding of arrestin proteins, and internalization of the receptor through clathrin-coated pits. Despite mediating a cornucopia of physiological processes, the role of GPCRs in tumor biology is underappreciated. GPCRs, their ligands, and downstream effectors significantly regulate tumor growth and metastasis but influence tumor and stromal cells alike. The normal physiological functions of GPCRs are often hijacked by malignant cells to promote cell survival and proliferation, immune cell evasion, local and distant invasion, and recruitment of blood vessels.

This Special Issue of Cells invites both original research and review articles that examine the role of GPCRs, their G-protein targets and their regulatory apparatus (RGSs, GRKs) in tumorigenesis (including the role of point mutations, gene overexpression, and epigenetic promoter silencing), and stromal and immune responses in the tumor milieu. We will also discuss the unique opportunities for targeting GPCRs for therapeutic gain in cancers without current therapy and those refractory to current approaches.

Dr. Anthony Ashton
Guest Editor

Manuscript Submission Information

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Keywords

  • GPCR
  • arrestin
  • RGS
  • GRK
  • tumorigenesis
  • inflammation
  • angiogenesis
  • metastasis

Published Papers (4 papers)

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Research

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Article
Expression of Proton-Sensitive GPR31, GPR151, TASK1 and TASK3 in Common Skin Tumors
Cells 2022, 11(1), 27; https://doi.org/10.3390/cells11010027 - 23 Dec 2021
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Abstract
TWIK-related acid-sensitive potassium channels TASK1 and TASK3, as well as the G-protein-coupled receptors GPR31 and GPR151, are proton-sensitive membrane proteins. They can be activated or inhibited by low extracellular pH (pHe), which is a hallmark of the tumor microenvironment in solid tumors. However, [...] Read more.
TWIK-related acid-sensitive potassium channels TASK1 and TASK3, as well as the G-protein-coupled receptors GPR31 and GPR151, are proton-sensitive membrane proteins. They can be activated or inhibited by low extracellular pH (pHe), which is a hallmark of the tumor microenvironment in solid tumors. However, the role of these channels in the development of skin tumors is still unclear. In this study, we investigated the expression profiles of TASK1, TASK3, GPR31 and GPR151 in squamous cell carcinomas (SCCs), basal cell carcinomas (BCCs), nevus cell nevi (NCN), and malignant melanomas (MMs). We performed immunohistochemistry using paraffin-embedded tissue samples from patients and found that most skin tumors express TASK1/3 and GPR31/151. The results show that BCCs are often negative for GPR31/151 as well as for TASK1/3, while nearly all SCCs express these markers. MMs and NCN show similar expression patterns. However, some tumors show a decreasing TASK1/3 expression in deeper dermal tumor tissue, while GPCRs were expressed more evenly. The lower frequency of GPR31/151 and TSAK1/3 expression in BCCs when compared to SCCs is a novel histological feature distinguishing these two entities. Moreover, BCCs also show lower expression of GPR31/151 and TASK1/3 as compared to NCN and MMs. Full article
(This article belongs to the Special Issue G-Protein Coupled Receptors in Cancer)
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Review

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Review
Role of ADGRG1/GPR56 in Tumor Progression
Cells 2021, 10(12), 3352; https://doi.org/10.3390/cells10123352 - 29 Nov 2021
Viewed by 329
Abstract
Cellular communication plays a critical role in diverse aspects of tumorigenesis including tumor cell growth/death, adhesion/detachment, migration/invasion, angiogenesis, and metastasis. G protein-coupled receptors (GPCRs) which constitute the largest group of cell surface receptors are known to play fundamental roles in all these processes. [...] Read more.
Cellular communication plays a critical role in diverse aspects of tumorigenesis including tumor cell growth/death, adhesion/detachment, migration/invasion, angiogenesis, and metastasis. G protein-coupled receptors (GPCRs) which constitute the largest group of cell surface receptors are known to play fundamental roles in all these processes. When considering the importance of GPCRs in tumorigenesis, the adhesion GPCRs (aGPCRs) are unique due to their hybrid structural organization of a long extracellular cell-adhesive domain and a seven-transmembrane signaling domain. Indeed, aGPCRs have been increasingly shown to be associated with tumor development by participating in tumor cell interaction and signaling. ADGRG1/GPR56, a representative tumor-associated aGPCR, is recognized as a potential biomarker/prognostic factor of specific cancer types with both tumor-suppressive and tumor-promoting functions. We summarize herein the latest findings of the role of ADGRG1/GPR56 in tumor progression. Full article
(This article belongs to the Special Issue G-Protein Coupled Receptors in Cancer)
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Review
An Insight into GPCR and G-Proteins as Cancer Drivers
Cells 2021, 10(12), 3288; https://doi.org/10.3390/cells10123288 - 24 Nov 2021
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Abstract
G-protein-coupled receptors (GPCRs) are the largest family of cell surface signaling receptors known to play a crucial role in various physiological functions, including tumor growth and metastasis. Various molecules such as hormones, lipids, peptides, and neurotransmitters activate GPCRs that enable the coupling of [...] Read more.
G-protein-coupled receptors (GPCRs) are the largest family of cell surface signaling receptors known to play a crucial role in various physiological functions, including tumor growth and metastasis. Various molecules such as hormones, lipids, peptides, and neurotransmitters activate GPCRs that enable the coupling of these receptors to highly specialized transducer proteins, called G-proteins, and initiate multiple signaling pathways. Integration of these intricate networks of signaling cascades leads to numerous biochemical responses involved in diverse pathophysiological activities, including cancer development. While several studies indicate the role of GPCRs in controlling various aspects of cancer progression such as tumor growth, invasion, migration, survival, and metastasis through its aberrant overexpression, mutations, or increased release of agonists, the explicit mechanisms of the involvement of GPCRs in cancer progression is still puzzling. This review provides an insight into the various responses mediated by GPCRs in the development of cancers, the molecular mechanisms involved and the novel pharmacological approaches currently preferred for the treatment of cancer. Thus, these findings extend the knowledge of GPCRs in cancer cells and help in the identification of therapeutics for cancer patients. Full article
(This article belongs to the Special Issue G-Protein Coupled Receptors in Cancer)
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Review
Adenosine Receptor Antagonists to Combat Cancer and to Boost Anti-Cancer Chemotherapy and Immunotherapy
Cells 2021, 10(11), 2831; https://doi.org/10.3390/cells10112831 - 21 Oct 2021
Viewed by 521
Abstract
Extracellular adenosine accumulates in the environment of numerous tumors. For years, this fact has fueled preclinical research to determine whether adenosine receptors (ARs) could be the target to fight cancer. The four ARs discovered so far, A1, A2A, A [...] Read more.
Extracellular adenosine accumulates in the environment of numerous tumors. For years, this fact has fueled preclinical research to determine whether adenosine receptors (ARs) could be the target to fight cancer. The four ARs discovered so far, A1, A2A, A2B and A3, belong to the class A family of G protein-coupled receptors (GPCRs) and all four have been involved in one way or another in regulating tumor progression. Prompted by the successful anti-cancer immunotherapy, the focus was placed on the ARs more involved in regulation of immune cell differentiation and activation and that are able to establish molecular and functional interactions. This review focuses on the potential of A2A and A2B receptor antagonists in cancer control and in boosting anti-cancer chemotherapy and immunotherapy. The article also overviews the ongoing clinical trials in which A2AR and A2BR ligands are being tested in anti-cancer therapy. Full article
(This article belongs to the Special Issue G-Protein Coupled Receptors in Cancer)
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