scholarly journals CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1706
Author(s):  
Chih-Lun Cheng ◽  
Shang-Chih Yang ◽  
Chien-Ying Lai ◽  
Cheng-Kai Wang ◽  
Ching-Fang Chang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Receptor Tyrosine Kinase ◽  
Cell Biology ◽  
Embryonic Stem ◽  
G Protein Coupled Receptors ◽  
Cell Cycle Distribution ◽  
Self Renewal ◽  
Inflammatory Protein ◽  
G Protein Coupled ◽  
Macrophage Inflammatory Protein

Human embryonic stem cells (hESCs) have important roles in regenerative medicine, but only a few studies have investigated the cytokines secreted by hESCs. We screened and identified chemokine (C-X-C motif) ligand 14 (CXCL14), which plays crucial roles in hESC renewal. CXCL14, a C-X-C motif chemokine, is also named as breast and kidney-expressed chemokine (BRAK), B cell and monocyte-activated chemokine (BMAC), and macrophage inflammatory protein-2γ (MIP-2γ). Knockdown of CXCL14 disrupted the hESC self-renewal, changed cell cycle distribution, and further increased the expression levels of mesoderm and endoderm differentiated markers. Interestingly, we demonstrated that CXCL14 is the ligand for the insulin-like growth factor 1 receptor (IGF-1R), and it can activate IGF-1R signal transduction to support hESC renewal. Currently published literature indicates that all receptors in the CXCL family are G protein-coupled receptors (GPCRs). This report is the first to demonstrate that a CXCL protein can bind to and activate a receptor tyrosine kinase (RTK), and also the first to show that IGF-1R has another ligand in addition to IGFs. These findings broaden our understanding of stem cell biology and signal transduction.

scholarly journals The CCL20-CCR6 Axis in Cancer Progression

2020 ◽  
Vol 21 (15) ◽  
pp. 5186 ◽  
Author(s):  
Suguru Kadomoto ◽  
Kouji Izumi ◽  
Atsushi Mizokami
Keyword(s):  
Cancer Progression ◽  
Immune Cell ◽  
G Protein Coupled Receptors ◽  
Virus Infections ◽  
Cancer Breast ◽  
Inflammatory Protein ◽  
Immunodeficiency Virus ◽  
G Protein Coupled ◽  
Macrophage Inflammatory Protein

Chemokines, which are basic proteins that exert their effects via G protein-coupled receptors and a subset of the cytokine family, are mediators deeply involved in leukocyte migration during an inflammatory reaction. Chemokine (C-C motif) ligand 20 (CCL20), also known as macrophage inflammatory protein (MIP)-3α, liver activation regulated chemokine (LARC), and Exodus-1, is a small protein that is physiologically expressed in the liver, colon, and skin, is involved in tissue inflammation and homeostasis, and has a specific receptor C-C chemokine receptor 6 (CCR6). The CCL20-CCR6 axis has long been known to be involved in inflammatory and infectious diseases, such as rheumatoid arthritis and human immunodeficiency virus infections. Recently, however, reports have shown that the CCL20-CCR6 axis is associated with several cancers, including hepatocellular carcinoma, colorectal cancer, breast cancer, pancreatic cancer, cervical cancer, and kidney cancer. The CCL20-CCR6 axis promotes cancer progression directly by enhancing migration and proliferation of cancer cells and indirectly by remodeling the tumor microenvironment through immune cell control. The present article reviewed the role of the CCL20-CCR6 axis in cancer progression and its potential as a therapeutic target.

scholarly journals Human Herpesvirus 7 Open Reading Frame U12 Encodes a Functional β-Chemokine Receptor

2003 ◽  
Vol 77 (14) ◽  
pp. 8108-8115 ◽  
Author(s):  
Kazushi Nakano ◽  
Kenjiro Tadagaki ◽  
Yuji Isegawa ◽  
Mya Mya Aye ◽  
Ping Zou ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Biological Function ◽  
Human Herpesvirus ◽  
G Protein Coupled Receptors ◽  
Biological Functions ◽  
Reading Frame ◽  
Inflammatory Protein ◽  
G Protein Coupled ◽  
Macrophage Inflammatory Protein

ABSTRACT Human herpesvirus 7 (HHV-7), which belongs to the betaherpesvirus subfamily, infects mainly CD4+ T cells in vitro and infects children during infancy. After the primary infection, HHV-7 becomes latent. HHV-7 contains two genes (U12 and U51) that encode putative homologs of cellular G-protein-coupled receptors. To analyze the biological function of the U12 gene, we cloned the gene and expressed the U12 protein in cells. The U12 gene encoded a calcium-mobilizing receptor for the EBI1 ligand chemokine-macrophage inflammatory protein 3β (ELC/MIP-3β) but not for other chemokines, suggesting that the chemokine selectivity of the U12 gene product is distinct from that of the known mammalian chemokine receptors. These studies revealed that U12 activates distinct transmembrane signaling pathways that may mediate biological functions by binding with a β-chemokine, ELC/MIP-3β.

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 formyl peptide receptors play a dual role in neutrophil chemotaxis and bacterial phagocytosis

2019 ◽  
Vol 30 (3) ◽  
pp. 346-356 ◽  
Author(s):  
Xi Wen ◽  
Xuehua Xu ◽  
Wenxiang Sun ◽  
Keqiang Chen ◽  
Miao Pan ◽  
...  
Keyword(s):  
G Protein ◽  
Receptor Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Actin Polymerization ◽  
G Protein Coupled Receptors ◽  
Peptide Receptors ◽  
Tyrosine Kinase Signaling ◽  
Formyl Peptide Receptors ◽  
Formyl Peptide ◽  
G Protein Coupled

A dogma of innate immunity is that neutrophils use G-protein–coupled receptors (GPCRs) for chemoattractant to chase bacteria through chemotaxis and then use phagocytic receptors coupled with tyrosine kinases to destroy opsonized bacteria via phagocytosis. Our current work showed that G-protein–coupled formyl peptide receptors (FPRs) directly mediate neutrophil phagocytosis. Mouse neutrophils lacking formyl peptide receptors (Fpr1/2–/–) are defective in the phagocytosis of Escherichia coli and the chemoattractant N-formyl-Met-Leu-Phe (fMLP)-coated beads. fMLP immobilized onto the surface of a bead interacts with FPRs, which trigger a Ca2+response and induce actin polymerization to form a phagocytic cup for engulfment of the bead. This chemoattractant GPCR/Gi signaling works independently of phagocytic receptor/tyrosine kinase signaling to promote phagocytosis. Thus, in addition to phagocytic receptor-mediated phagocytosis, neutrophils also utilize the chemoattractant GPCR/Gi signaling to mediate phagocytosis to fight against invading bacteria.

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.

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