GPRC5A: An Emerging Biomarker in Human Cancer

Jiang, Xiaoxia; Xu, Xin; Wu, Mengjie; Guan, Zhonghai; Su, Xingyun; Chen, Shitu; Teng, Lisong

doi:10.1155/2018/1823726

Cited by 33 publications

(36 citation statements)

References 96 publications

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“…Many observations have highlighted a strong connection between alterations in GPRC5A and several human cancers (Jiang et al, 2018), and in particular with the presence of more aggressive and metastatic phenotypes through the induction of the EMT Sawada et al, 2020;Liu et al, 2017). EMT takes place physiologically during embryonic development, tissue regeneration, organ fibrosis, and wound healing.…”

Section: Discussionmentioning

confidence: 99%

Autoregulatory circuit regulating basolateral cargo export from the TGN: role of the orphan receptor GPRC5A in PKD signaling and cell polarity

Martino

Capalbo

Sticco

et al. 2020

Preprint

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The membrane transport apparatus comprises a series of separate membrane bound compartments, or transport stations, that are responsible for the synthesis, processing, transport, sorting and delivery to their final cellular destinations of most transmembrane and soluble lumenal proteins. Over the last decades the membrane transport system has been shown to be extensively regulated both by environmental inputs and by internal homeostatic signalling systems, or control systems, that operate to maintain the homeostasis and optimal functionality of the main transport stations, such as the endoplasmic reticulum and the Golgi, in the face of internal and external perturbations. The trans-Golgi network (TGN) is a major transport and processing station and the main sorting compartment of the transport apparatus. However, the mechanisms that control cargo export and sorting at the TGN have so far remained elusive. Here we focus on the sorting of basolateral cargo proteins and show that these proteins bind to the TGN localized orphan receptor GPRC5A. The cargo-GPRC5A complex triggers the activation of a signaling pathway that involves the Gβγ subunits dependent activation of the phospholipase C beta 3 (PLCβ3), which inturn induces diacyl glycerol (DAG) production. DAG recruits and activates protein kinase D (PKD) and the phosphorylation of its substrates. This step results in the formation of basolateral carriers for delivery of these cargoes to the basolateral plasma membrane domain. We term this mechanism "ARTG" (AutoRegulation of TGN export). Remarkably, the impairment of ARTG pathway components, and in particular of GPRC5A, causes defects in the polarized organization of epithelial cells.

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Section: Discussionmentioning

confidence: 99%

Autoregulatory circuit regulating basolateral cargo export from the TGN: role of the orphan receptor GPRC5A in PKD signaling and cell polarity

Martino

Capalbo

Sticco

et al. 2020

Preprint

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“…GPCRomics may identify GPCRs amenable to such approaches and may help guide appropriate hiPSC-derived models for drug screening and perhaps, cell therapy. Newly recognized GPCRs may also be useful as biomarkers that can be analyzed on circulating (tumor, fetal) cells, exosomes in the blood or urine or as cell surface proteins detectable with antibodies or other probes, perhaps via imaging methods [32,[84][85][86][87][88][89]. Such techniques may further facilitate personalized/precision medicine approaches for GPCR therapeutics: identification of individual and groups of patients who express one or more GPCRs that can be treated with appropriate GPCR-targeted agents and whose response is monitored by biomarker analyses.…”

Section: Resultsmentioning

confidence: 99%

GPCRomics: An Approach to Discover GPCR Drug Targets

Insel

Sriram

Gorr

et al. 2019

Trends in Pharmacological Sciences

138

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G protein-coupled receptors (GPCRs) are targets for ~35% of approved drugs but only ~15% of the ~800 human GPCRs are currently such targets. GPCRomics, the use of unbiased, hypothesisgenerating methods (e.g., RNA-sequencing [RNA-seq]), with tissues and cell types to identify and quantify GPCR expression, has led to the discovery of previously unrecognized GPCRs that contribute to functional responses and pathophysiology and that may be therapeutic targets. The combination of GPCR expression data with validation studies (e.g., signaling and functional activities) provides opportunities for the discovery of disease-relevant GPCR targets and therapeutics. Here, we review insights from GPCRomic approaches, gaps in knowledge and future directions by which GPCRomics can advance GPCR biology and the discovery of new GPCRtargeted drugs.

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“…Another protein present in the media from five conceptuses (heavy labelled in CCM from three conceptuses) is GPRC5A. This protein belongs to a group of receptors and has been found to be dysregulated in cancer [51] and is a lung cancer suppressor gene [52]. In GPRC5A-knock out mice, prostaglandin E2 synthase (PTGES)/prostaglandin E2 (PGE2) signaling is highly associated with tumorigenesis and metastasis and is related to immune suppression in lung cancer [52].…”

Section: De Novo Synthesised Proteins In Conceptus-conditioned Mediamentioning

confidence: 99%

Protein Synthesis by Day 16 Bovine Conceptuses during the Time of Maternal Recognition of Pregnancy

Estepa

Tinning

Vasconcelos

et al. 2020

IJMS

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Interferon Tau (IFNT), the conceptus-derived pregnancy recognition signal in cattle, significantly modifies the transcriptome of the endometrium. However, the endometrium also responds to IFNT-independent conceptus-derived products. The aim of this study was to determine what proteins are produced by the bovine conceptus that may facilitate the pregnancy recognition process in cattle. We analysed by mass spectrometry the proteins present in conceptus-conditioned media (CCM) after 6 h culture of Day 16 bovine conceptuses (n = 8) in SILAC media (arginine- and lysine-depleted media supplemented with heavy isotopes) and the protein content of extracellular vesicles (EVs) isolated from uterine luminal fluid (ULF) of Day 16 pregnant (n = 7) and cyclic (n = 6) cross-bred heifers on day 16. In total, 11,122 proteins were identified in the CCM. Of these, 5.95% (662) had peptides with heavy labelled amino acids, i.e., de novo synthesised by the conceptuses. None of these proteins were detected in the EVs isolated from ULF. Pregnancy-associated glycoprotein 11, Trophoblast Kunitz domain protein 1 and DExD-Box Helicase 39A were de novo produced and present in the CCM from all conceptuses and in previously published CCM data following 6 and 24 h. A total of 463 proteins were present in the CCM from all the conceptuses in the present study, and after 6 and 24 h culture in a previous study, while expression of their transcripts was not detected in endometrium indicating that they are likely conceptus-derived. Of the proteins present in the EVs, 67 were uniquely identified in ULF from pregnant heifers; 35 of these had been previously reported in CCM from Day 16 conceptuses. This study has narrowed a set of conceptus-derived proteins that may be involved in EV-mediated IFNT-independent embryo–maternal communication during pregnancy recognition in cattle.

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GPRC5A: An Emerging Biomarker in Human Cancer

Cited by 33 publications

References 96 publications

Autoregulatory circuit regulating basolateral cargo export from the TGN: role of the orphan receptor GPRC5A in PKD signaling and cell polarity

Autoregulatory circuit regulating basolateral cargo export from the TGN: role of the orphan receptor GPRC5A in PKD signaling and cell polarity

GPCRomics: An Approach to Discover GPCR Drug Targets

Protein Synthesis by Day 16 Bovine Conceptuses during the Time of Maternal Recognition of Pregnancy

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