G Protein-Coupled Receptors in radioiodine-refractory thyroid cancer in the Era of Precision Medicine

2021 ◽  
Author(s):  
Valentine Suteau ◽  
Valérie Seegers ◽  
Mathilde Munier ◽  
Rym Ben Boubaker ◽  
Cécile Reyes ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Precision Medicine ◽  
Mrna Expression ◽  
G Protein ◽  
Cell Biology ◽  
Drug Repositioning ◽  
G Protein Coupled Receptors ◽  
Bioinformatics Analyses ◽  
Thyroid Cancers ◽  
G Protein Coupled

Abstract Context Radioiodine-refractory thyroid cancers have poor outcomes and limited therapeutic options, i.e tyrosine kinase inhibitors, due to transient efficacy and toxicity of treatments. Therefore, combinatorial treatments with new therapeutic approaches are needed. Many studies link G Protein-Coupled Receptors (GPCRs) to cancer cell biology. Objective To perform a specific atlas of GPCRs expression in progressive and refractory thyroid cancer to identify potential targets among GPCRs aiming at drug repositioning. Method We analyzed samples from tumor and normal thyroid tissues from 17 patients with refractory thyroid cancer (twelve papillary thyroid cancers (PTC) and five follicular thyroid cancers (FTC)). We assessed the GPCR mRNA expression using the NanoString technology with a custom panel of 371 GPCRs. The data were compared with public repositories and pharmacological databases to identify eligible drugs. The analysis of prognostic value of genes was also performed with TCGA datasets. Results With our transcriptomic analysis, 4 receptors were found down regulated in FTC (VIPR1, ADGRL2/LPHN2, ADGRA3 and ADGRV1). In PTC, 24 receptors were deregulated, seven of which identified also by bioinformatics analyses of publicly available dataset on primary thyroid cancers (VIPR1, ADORA1, GPRC5B, P2RY8, GABBR2, CYSLTR2 and LPAR5). Among all the differentially expressed genes, 22 GPCRs are the target of approved drugs and some GPCRs were also associated with prognostic factors. Conclusions For the first time, we performed GPCR mRNA expression profiling in progressive and refractory thyroid cancers. These findings provide an opportunity to identify potential therapeutic targets for drug repositioning and precision medicine in radioiodine-refractory thyroid cancer.

Recent Advances of Small Molecular Regulators Targeting G Protein- Coupled Receptors Family for Oncology Immunotherapy

2019 ◽  
Vol 19 (16) ◽  
pp. 1464-1483 ◽  
Author(s):  
Peng He ◽  
Wenbo Zhou ◽  
Mingyao Liu ◽  
Yihua Chen
Keyword(s):  
G Protein ◽  
Cell Biology ◽  
Immune Cell ◽  
G Protein Coupled Receptors ◽  
Treatment Modalities ◽  
Immune Checkpoints ◽  
Considerable Proportion ◽  
Prostaglandin E ◽  
Recent Advances ◽  
G Protein Coupled

The great clinical success of chimeric antigen receptor T cell (CAR-T) and PD-1/PDL-1 inhibitor therapies suggests the drawing of a cancer immunotherapy age. However, a considerable proportion of cancer patients currently receive little benefit from these treatment modalities, indicating that multiple immunosuppressive mechanisms exist in the tumor microenvironment. In this review, we mainly discuss recent advances in small molecular regulators targeting G Protein-Coupled Receptors (GPCRs) that are associated with oncology immunomodulation, including chemokine receptors, purinergic receptors, prostaglandin E receptor EP4 and opioid receptors. Moreover, we outline how they affect tumor immunity and neoplasia by regulating immune cell recruitment and modulating tumor stromal cell biology. We also summarize the data from recent clinical advances in small molecular regulators targeting these GPCRs, in combination with immune checkpoints blockers, such as PD-1/PDL-1 and CTLA4 inhibitors, for cancer treatments.

scholarly journals G-Protein Coupled Receptors (GPCRs) in Insects—A Potential Target for New Insecticide Development

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2993
Author(s):  
Nannan Liu ◽  
Ting Li ◽  
Yifan Wang ◽  
Shikai Liu
Keyword(s):  
Insecticide Resistance ◽  
G Protein ◽  
Cell Biology ◽  
Insect Pest ◽  
Expression Patterns ◽  
G Protein Coupled Receptors ◽  
Insect Physiology ◽  
Cell Functions ◽  
Specific Distribution ◽  
G Protein Coupled

G-protein coupled receptors (GPCRs) play important roles in cell biology and insects’ physiological processes, toxicological response and the development of insecticide resistance. New information on genome sequences, proteomic and transcriptome analysis and expression patterns of GPCRs in organs such as the central nervous system in different organisms has shown the importance of these signaling regulatory GPCRs and their impact on vital cell functions. Our growing understanding of the role played by GPCRs at the cellular, genome, transcriptome and tissue levels is now being utilized to develop new targets that will sidestep many of the problems currently hindering human disease control and insect pest management. This article reviews recent work on the expression and function of GPCRs in insects, focusing on the molecular complexes governing the insect physiology and development of insecticide resistance and examining the genome information for GPCRs in two medically important insects, mosquitoes and house flies, and their orthologs in the model insect species Drosophila melanogaster. The tissue specific distribution and expression of the insect GPCRs is discussed, along with fresh insights into practical aspects of insect physiology and toxicology that could be fundamental for efforts to develop new, more effective, strategies for pest control and resistance management.

scholarly journals Immunohistochemical detection, regulation and antiproliferative function of G-protein-coupled receptor kinase 2 in thyroid carcinomas

2008 ◽  
Vol 198 (1) ◽  
pp. 101-110 ◽  
Author(s):  
Thierry Métayé ◽  
Pierre Levillain ◽  
Jean-Louis Kraimps ◽  
Rémy Perdrisot
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Enzymatic Activity ◽  
G Protein ◽  
Human Thyroid ◽  
G Protein Coupled Receptor ◽  
Thyroid Cancers ◽  
Normal Tissues ◽  
Igf I ◽  
G Protein Coupled

TSH, via its G-protein-coupled receptor, activates cell growth of both benign and malignant thyroid tumors. G-protein-coupled receptors (GR) kinase 2 (GRK2) has been reported to regulate the TSH receptor but its role in cancer is unknown. To determine a possible function for GRK2 in the growth process of thyroid cancers, we analysed its expression in normal and tumoral thyroid tissues and studied thyroid cancer cell line proliferation after GRK2 overexpression. Thirty one thyroid tissues, including 16 non-medullary thyroid cancers and 15 adjacent normal tissues, were analysed by immunohistochemistry. Five paired tissues were also studied by western blotting for the GRK2 enzymatic activity. Immunohistochemical staining showed an increase in GRK2 in thyroid cancers including papillary, follicular, and anaplastic types, compared with their adjacent normal tissues. Immunoblot analysis and GRK2 enzymatic activity measurement confirmed immunohistochemical study. TSH and TSH in association with insulin or IGF-I stimulated GRK2 protein accumulation in normal human thyroid cells in primary culture. The TSH effect on the GRK2 expression was mimicked by forskolin. After GRK2 overexpression in two poorly differentiated thyroid cell lines, all the clones showed a significant reduction in cell proliferation, ranging from 28 to 65% inhibition compared with vector alone after 96-h culture. In conclusion, thyroid mitogenic factor-stimulated GRK2 accumulation may explain, in part, high GRK2 levels in differentiated carcinoma, because TSH, insulin, or IGF-I is known to be involved in the thyroid cancer progression. Surprisingly, instead of stimulating, GRK2 reduced cell proliferation revealing a new role for this kinase in the growth of thyroid cancers.

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