Role of ADGRG1/GPR56 in Tumor Progression

Ng, Kwai‐Fong; Chen, Tse–Ching; Stacey, Martin; Lin, Hsi‐Hsien

doi:10.3390/cells10123352

Cited by 11 publications

(4 citation statements)

References 105 publications

(199 reference statements)

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“…Furthermore, we identi ed subgroups of genes that may contribute to nintedanib resistance. Correlation analysis with lung function suggested that the gene ADGRG1 may be responsible for nintedanib resistance.ADGRG1/GPR56 is a type of tumorassociated aGPCR that is thought to be a potential biomarker and prognostic factor for speci c cancer types due to its tumor-inhibitory and tumor-promoting functions (54).However, our analysis using the TCGA database did not show a correlation between ADGRG1 and survival in lung cancer patients. This suggests that there could be differences in the treatment effects of ADGRG1 and nintedanib, highlighting the need for further research in this area.…”

Section: Discussioncontrasting

confidence: 55%

Expression profiles of nintedanib-targeting molecules in progressive fibrotic interstitial lung diseases (non-IPF-PF) and IPF

Zhang

Wang

et al. 2023

Preprint

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Background: Idiopathic pulmonary fibrosis (IPF) and other types of progressive fibrotic interstitial lung diseases (non-IPF-PF), such as chronic hypersensitivity pneumonitis (cHP), systemic sclerosis (SSc), non-specific interstitial pneumonia (NSIP), and sarcoidosis, are common interstitial lung diseases. Nintedanib is one of the two approved therapies that can significantly slow the progression of IPF. However, the potential of nintedanib in non-IPF-PF has not been fully evaluated. Methods: We reanalyzed the single-cell data of IPF and non-IPF-PF and identified the main target genes of nintedanib (FGFR1, FGFR2, FGFR3, FLT1, FLT4, KDR, and PDGFRA) by subgroup classification and functional analysis of gene expression profiles in both IPF and non-IPF-PF. Results: We found that the main target genes of nintedanib were upregulated in IPF and various cell subpopulations of non-IPF-PF, including cHP, SSc, NSIP, and sarcoidosis, with Fgfr1 being the most elevated subpopulation. In fibroblasts, Fgfr1 was found to be elevated in both IPF and cHP. We identified nintedanib-sensitive cell subpopulations by analyzing the expression profiles of fibroblasts after nintedanib treatment. We also found that nintedanib could inhibit the nintedanib-sensitive gene set in mice treated with nintedanib in vivo. Furthermore, we demonstrated that key regulatory genes of nintedanib were positively correlated with survival in lung adenocarcinoma, providing further support for the potential anti-tumor activity of nintedanib in vivo. Conclusion: Our findings provide comprehensive evidence of the target expression of nintedanib in non-IPF-PF and IPF, highlighting the potential of nintedanib for the treatment of non-IPF-PF.

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Section: Discussioncontrasting

confidence: 55%

Expression profiles of nintedanib-targeting molecules in progressive fibrotic interstitial lung diseases (non-IPF-PF) and IPF

Zhang

Wang

et al. 2023

Preprint

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“…Supported by earlier knock-out studies [ 17 , 27 , 30 , 32 ] and the evaluation of multiple mouse genes in collagen-dependent thrombus formation in vivo and in vitro [ 14 ], our findings now add another element to the complex signaling cascades in platelets required for the build-up of a stable contracted thrombus. Our work also extends the multitude of functions of GPR56 in immune regulation and tumor progression [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 54%

Roles of Focal Adhesion Kinase PTK2 and Integrin αIIbβ3 Signaling in Collagen- and GPVI-Dependent Thrombus Formation under Shear

Huang

Jooss

Fernández

et al. 2022

IJMS

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Glycoprotein (GP)VI and integrin αIIbβ3 are key signaling receptors in collagen-dependent platelet aggregation and in arterial thrombus formation under shear. The multiple downstream signaling pathways are still poorly understood. Here, we focused on disclosing the integrin-dependent roles of focal adhesion kinase (protein tyrosine kinase 2, PTK2), the shear-dependent collagen receptor GPR56 (ADGRG1 gene), and calcium and integrin-binding protein 1 (CIB1). We designed and synthetized peptides that interfered with integrin αIIb binding (pCIB and pCIBm) or mimicked the activation of GPR56 (pGRP). The results show that the combination of pGRP with PTK2 inhibition or of pGRP with pCIB > pCIBm in additive ways suppressed collagen- and GPVI-dependent platelet activation, thrombus buildup, and contraction. Microscopic thrombus formation was assessed by eight parameters (with script descriptions enclosed). The suppressive rather than activating effects of pGRP were confined to blood flow at a high shear rate. Blockage of PTK2 or interference of CIB1 no more than slightly affected thrombus formation at a low shear rate. Peptides did not influence GPVI-induced aggregation and Ca2+ signaling in the absence of shear. Together, these data reveal a shear-dependent signaling axis of PTK2, integrin αIIbβ3, and CIB1 in collagen- and GPVI-dependent thrombus formation, which is modulated by GPR56 and exclusively at high shear. This work thereby supports the role of PTK2 in integrin αIIbβ3 activation and signaling.

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“…Besides, ZAR1L has been suggested potential associated with tumor suppressors, which can repress the transcription of BACA2 to repress breast cancer cells 41 . ADGRG1 (GPR56) is a representative tumor-related G protein-coupled receptors (GPCRs) member, which plays an important role in tumor cell growth, migration, angiogenesis, and metastasis 42,43 . AK7 is known to maintain ciliary structure and function whose dysfunction may lead to primary ciliary dyskinesia including bronchiectasis and reduced fertility [44][45][46] .…”

Section: Discussionmentioning

confidence: 99%

Former smoking associated with epigenetic modifications in human granulosa cells among women undergoing assisted reproduction

Tang,

Gaskins,

Hood

et al. 2024

Sci Rep

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Smoking exposure during adulthood can disrupt oocyte development in women, contributing to infertility and possibly adverse birth outcomes. Some of these effects may be reflected in epigenome profiles in granulosa cells (GCs) in human follicular fluid. We compared the epigenetic modifications throughout the genome in GCs from women who were former (N = 15) versus never smokers (N = 44) undergoing assisted reproductive technologies (ART). This study included 59 women undergoing ART. Smoking history including time since quitting was determined by questionnaire. GCs were collected during oocyte retrieval and DNA methylation (DNAm) levels were profiled using the Infinium MethylationEPIC BeadChip. We performed an epigenome-wide association study with robust linear models, regressing DNAm level at individual loci on smoking status, adjusting for age, ovarian stimulation protocol, and three surrogate variables. We performed differentially methylated regions (DMRs) analysis and over-representation analysis of the identified CpGs and corresponding gene set. 81 CpGs were differentially methylated among former smokers compared to never smokers (FDR < 0.05). We identified 2 significant DMRs (KCNQ1 and RHBDD2). The former smoking-associated genes were enriched in oxytocin signaling, adrenergic signaling in cardiomyocytes, platelet activation, axon guidance, and chemokine signaling pathway. These epigenetic variations have been associated with inflammatory responses, reproductive outcomes, cancer development, neurodevelopmental disorder, and cardiometabolic health. Secondarily, we examined the relationships between time since quitting and DNAm at significant CpGs. We observed three CpGs in negative associations with the length of quitting smoking (p < 0.05), which were cg04254052 (KCNIP1), cg22875371 (OGDHL), and cg27289628 (LOC148145), while one in positive association, which was cg13487862 (PLXNB1). As a pilot study, we demonstrated epigenetic modifications associated with former smoking in GCs. The study is informative to potential biological pathways underlying the documented association between smoking and female infertility and biomarker discovery for smoking-associated reproductive outcomes.

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Role of ADGRG1/GPR56 in Tumor Progression

Cited by 11 publications

References 105 publications

Expression profiles of nintedanib-targeting molecules in progressive fibrotic interstitial lung diseases (non-IPF-PF) and IPF

Expression profiles of nintedanib-targeting molecules in progressive fibrotic interstitial lung diseases (non-IPF-PF) and IPF

Roles of Focal Adhesion Kinase PTK2 and Integrin αIIbβ3 Signaling in Collagen- and GPVI-Dependent Thrombus Formation under Shear

Former smoking associated with epigenetic modifications in human granulosa cells among women undergoing assisted reproduction

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