Signaling via G proteins mediates tumorigenic effects of GPR87

Arfelt, Kristine Niss; Fares, Suzan; Sparre-Ulrich, Alexander Hovard; Hjortø, Gertrud Malene; Gasbjerg, Lærke S.; Mølleskov-Jensen, Ann-Sofie; Benned-Jensen, Tau

doi:10.1016/j.cellsig.2016.11.009

Cited by 23 publications

(21 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 28 , 29 Furthermore, Arfelt and colleagues documented the great relationship between the activation of NF-κB and GPR87-mediated cancer progression. 30 Because mTOR is involved in the liver metabolism process of a drug, 31 the balanced level of mTOR expression is vital for retaining hepatic cell homeostasis and prevention of liver damage and inflammation. Thus, the dysregulation of mTOR activity may result in liver injury, inflammation and even carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Vitamin E and Lactobacillus Provide Protective Effects Against Liver Injury Induced by HgCl₂: Role of CHOP, GPR87, and mTOR Proteins

et al. 2021

View full text Add to dashboard Cite

Background and Objective: Mercury is one of the most harmful heavy metals and its toxicity causes severe multi-organ dysfunction. This study was designed to explore novel molecular pathways involved in the hepatoprotective effect of vitamin E (Vit-E) and Lactobacillius plantarum (Lac-B) against mercury toxicity.[Formula: see text] Method: Acute hepatotoxicity was induced by administration of high dose of mercuric chloride (HgCl2) in male rats, Vit-E or/and Lac-B were given along with HgCl2 for 2 weeks. The effects of those antioxidants were studied focusing on their anti-apoptotic, anti-oxidative stress and anti-inflammatory eficacies. Histopathological examinations were also conducted. Results: The administration of HgCl2 induced liver injury which manifested by elevation in serum ALT and AST. Liver MDA, caspase-3 and TNF-α levels were markedly increased; whereas, GSH level and SOD activity were declined. HgCl2 significantly elevated the expressions of hepatic CHOP, GPR87, NF-κB and mTOR. Histopathological examination revealed massive hepatocyte degeneration following HgCl2 administration. Treatment with Vit-E or/and Lac-B restored the normal levels of the previously mentioned parameters, as well as improved hepatic architecture. Conclusion: Vit-E and Lac-B provided protective effect against HgCl2-induced hepatotoxicity via reduction of oxidative stress and inflammation, and downregulation of CHOP, GPR87, NF-κB and mTOR proteins’ expressions.

show abstract

Section: Discussionmentioning

confidence: 99%

Vitamin E and Lactobacillus Provide Protective Effects Against Liver Injury Induced by HgCl₂: Role of CHOP, GPR87, and mTOR Proteins

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The combination of an efficient DNA cloning strategy with the Flp-In system for stable cell line generation guarantees high utility of the vectors. The Flp-In system is widely used in different research areas, like mitochondria [ 108 ], [ 109 ], [ 110 ], [ 111 ], [ 112 ], RNA metabolism [ 113 ], [ 114 ], [ 115 ], proteomic studies [ 116 ], [ 117 ], [ 118 ], cell signaling [ 119 ], [ 120 ] and others [ 121 ], which calls for the existence of compatible vectors that ensure straightforward cloning. The pKK-RNAi vectors have a high potential of being particularly useful in functional analyses.…”

Section: Discussionmentioning

confidence: 99%

Versatile approach for functional analysis of human proteins and efficient stable cell line generation using FLP-mediated recombination system

et al. 2018

View full text Add to dashboard Cite

Deciphering a function of a given protein requires investigating various biological aspects. Usually, the protein of interest is expressed with a fusion tag that aids or allows subsequent analyses. Additionally, downregulation or inactivation of the studied gene enables functional studies. Development of the CRISPR/Cas9 methodology opened many possibilities but in many cases it is restricted to non-essential genes. Recombinase-dependent gene integration methods, like the Flp-In system, are very good alternatives. The system is widely used in different research areas, which calls for the existence of compatible vectors and efficient protocols that ensure straightforward DNA cloning and generation of stable cell lines. We have created and validated a robust series of 52 vectors for streamlined generation of stable mammalian cell lines using the FLP recombinase-based methodology. Using the sequence-independent DNA cloning method all constructs for a given coding-sequence can be made with just three universal PCR primers. Our collection allows tetracycline-inducible expression of proteins with various tags suitable for protein localization, FRET, bimolecular fluorescence complementation (BiFC), protein dynamics studies (FRAP), co-immunoprecipitation, the RNA tethering assay and cell sorting. Some of the vectors contain a bidirectional promoter for concomitant expression of miRNA and mRNA, so that a gene can be silenced and its product replaced by a mutated miRNA-insensitive version. Our toolkit and protocols have allowed us to create more than 500 constructs with ease. We demonstrate the efficacy of our vectors by creating stable cell lines with various tagged proteins (numatrin, fibrillarin, coilin, centrin, THOC5, PCNA). We have analysed transgene expression over time to provide a guideline for future experiments and compared the effectiveness of commonly used inducers for tetracycline-responsive promoters. As proof of concept we examined the role of the exoribonuclease XRN2 in transcription termination by RNAseq.

show abstract

“…LPA is one of the most potent mitogens secreted in the tumor-associated environment including the ascites fluid produced by ovarian cancer cells, stimulating the LPA-sensitive GPCRs that are frequently overexpressed by these tumor cells and thus contributing growth, survival and resistance to chemotherapy [37]. Meanwhile, a recent study also showed that Gαi and Gαq contribute to GPR87-mediated NF-κB activation in the 293 T cells, which is ligand-independent [38], further support the notion that functional NF-κB activation is critical for GPR87-mediated cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of G protein-coupled receptor GPR87 promotes pancreatic cancer aggressiveness and activates NF-κB signaling pathway

et al. 2017

View full text Add to dashboard Cite

BackgroundPancreatic cancer is a highly lethal disease and has the worst prognosis of any major malignancy. G protein-coupled receptor GPR87 is reported to be overexpressed in multiple cancers. The clinical significance and biological role of GPR87 in pancreatic cancer, however, remain to be established.MethodsGPR87 expression in pancreatic cancer cell lines, paired patient tissues were determined using western blotting and Real-time PCR. Ninety-six human pancreatic cancer tissue samples were analyzed by immunochemistry (IHC) to investigate the association between GPR87 expression and the clinicopathological characteristics of pancreatic cancer. Functional assays, such as anchorage-independent growth, chicken chorioallantoic membrane (CAM) assay, transwell matrix penetration assay, and Annexin V-FITC and PI staining and a xenograft tumor model were used to determine the oncogenic role of GPR87 in human pancreatic cancer progression. The effect of GPR87 on NF-κB signaling pathway was further investigated using the luciferase reporter assays, and by detection of the NF-κB signaling downstream genes.ResultsHerein, we reported that GPR87 was markedly overexpressed in pancreatic cancer cells and clinical tissues. Immunohistochemical analysis showed that the expression of GPR87 significantly correlated with patients’ clinicopathologic features, including clinical stage and tumor-nodule-metastasis (TNM) classification. Pancreatic cancer patients with higher levels of GPR87 expression had shorter overall survival compared to patients with lower GPR87 levels. We gained valuable insights into the mechanism of GPR87 expression in pancreatic cancer cells by demonstrating that overexpressing GPR87 significantly enhanced, whereas silencing endogenous GPR87 inhibited, the proliferation, angiogenesis and increased resistance to gemcitabine-induced apoptosis of pancreatic cancer in vitro and tumorigenicity of pancreatic cancer cells in vivo. Finally, we demonstrated that GPR87 enhanced pancreatic cancer aggressiveness by activating NF-κB signaling pathway. Conclusions: Taken together, these findings suggest that GPR87 plays a critical oncogenic role in pancreatic cancer progression and highlight its potential as a target for pancreatic cancer therapy.ConclusionsOur findings suggest that GPR87 plays a critical oncogenic role in pancreatic cancer progression and highlight its potential as a target for pancreatic cancer therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0627-6) contains supplementary material, which is available to authorized users.

show abstract

Signaling via G proteins mediates tumorigenic effects of GPR87

Cited by 23 publications

References 50 publications

Vitamin E and Lactobacillus Provide Protective Effects Against Liver Injury Induced by HgCl₂: Role of CHOP, GPR87, and mTOR Proteins

Vitamin E and Lactobacillus Provide Protective Effects Against Liver Injury Induced by HgCl₂: Role of CHOP, GPR87, and mTOR Proteins

Versatile approach for functional analysis of human proteins and efficient stable cell line generation using FLP-mediated recombination system

Overexpression of G protein-coupled receptor GPR87 promotes pancreatic cancer aggressiveness and activates NF-κB signaling pathway

Contact Info

Product

Resources

About

Signaling via G proteins mediates tumorigenic effects of GPR87

Cited by 23 publications

References 50 publications

Vitamin E and Lactobacillus Provide Protective Effects Against Liver Injury Induced by HgCl2: Role of CHOP, GPR87, and mTOR Proteins

Vitamin E and Lactobacillus Provide Protective Effects Against Liver Injury Induced by HgCl2: Role of CHOP, GPR87, and mTOR Proteins

Versatile approach for functional analysis of human proteins and efficient stable cell line generation using FLP-mediated recombination system

Overexpression of G protein-coupled receptor GPR87 promotes pancreatic cancer aggressiveness and activates NF-κB signaling pathway

Contact Info

Product

Resources

About

Vitamin E and Lactobacillus Provide Protective Effects Against Liver Injury Induced by HgCl₂: Role of CHOP, GPR87, and mTOR Proteins

Vitamin E and Lactobacillus Provide Protective Effects Against Liver Injury Induced by HgCl₂: Role of CHOP, GPR87, and mTOR Proteins