Loss-of-Function Mutations in Calcitonin Receptor (<i>CALCR</i>) Identify Highly Aggressive Glioblastoma with Poor Outcome

Pal, Jagriti; Patil, Vikas; Kumar, Anupam; Kaur, Kavneet; Sarkar, Chitra; Somasundaram, Kumaravel

doi:10.1158/1078-0432.ccr-17-1901

Cited by 24 publications

(33 citation statements)

References 35 publications

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“…Analysis of the top two modules from the PPI network indicated that GBM was associated with the cell cycle and neuroactive ligand-receptor interaction. Pal et al (32) recently demonstrated that patients who have GBM in combination with a defective neuroactive ligand-receptor interaction pathway have a poor prognosis (P<0.0001). Therefore, monitoring these signaling pathways may help predict tumor occurrence and progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of hub genes and pathways in glioblastoma by bioinformatics analysis

Yang

Gao

2018

Oncol Lett

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Glioblastoma (GBM) is the most common type of malignant brain tumor, and is associated with poor patient prognosis. A comprehensive understanding of the molecular mechanism underlying GBM may help to guide the identification of novel diagnoses and treatment targets. The gene expression profile of the GSE4290 GBM dataset was analyzed in order to identify differentially expressed genes (DEGs). Enriched pathways were identified through Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses. A protein-protein interaction network was constructed in order to identify hub genes and for module analysis. Expression and survival analyses were conducted in order to screen and validate critical genes. A total of 1,801 DEGs were recorded, including 620 upregulated and 1,181 downregulated genes. Upregulated DEGs were enriched in the terms ‘mitotic cell cycle process’, ‘mitotic cell cycle’ and ‘cell cycle process’. Downregulated genes were enriched in ‘transsynaptic signaling’, ‘anterograde transsynaptic signaling’ and ‘synaptic signaling’. A total of 15 hub genes, which displayed a high degree of connectivity, were selected. These genes included vascular endothelial growth factor A, cyclin-dependent kinase 1 (CDK1), cell-division cycle protein 20 (CDC20), aurora kinase A (AURKA), and budding uninhibited by benzimidazoles 1 (BUB1). The identified DEGs and hub genes may help guide investigations on the mechanisms underlying the development and progression of GBM. CDK1, CDC20, AURKA and BUB1, which are involved in cell cycle pathways, may be potential targets in the diagnosis and therapy of GBM.

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Section: Discussionmentioning

confidence: 99%

Identification of hub genes and pathways in glioblastoma by bioinformatics analysis

Yang

Gao

2018

Oncol Lett

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“…Мутации в рецепторе кальцитонина (CALCR) выявляют высокоагрессивные глиобластомы с летальным результатом у человека. И все же можно констатировать, что экзогенно добавленный кальцитонин ингибировал различные свойства клеток глии и сигнальных путей рецептора [56].…”

Section: взаимодействие гормонов с рецепторамиunclassified

Breach of ligand-receptor interaction in pathogenesis of disadaptive disorders and in pathology

Артеменков

Александрович²

2019

Rev Clin Pharm Drug Ther

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The review summarizes information about the effects of ligand-receptor interaction in the normal state, during maladaptation and pathology. The mechanisms of changes in the functions of the receptors of the immune system that recognize pathogen patches, interact with immunoglobulins and participate in the immune response are shown. Data on interactions within the neurotransmitter systems of the brain are presented. The properties of lectins, follicle-stimulating hormone, progesterone derivatives and calcitonin are considered. The review also summarizes information on such cellular processes as cell growth, bone regeneration and remodeling, apoptosis. The role of thiazole retinoids in the regulation of cell differentiation and signaling pathways has been shown. Particular attention is paid to angiogenesis and vascular endothelial growth factor, receptors and ligands to fibroblast growth factor, galactins involved in oncotransformation processes. It was established that phosphatase with the Src2 homology domain (SHP2) is an important component of oncogenic signaling pathways. The mechanism of multivalent interaction of bacteria and viruses with the cells of the body is discussed. The interaction of nanoparticles (graphene, fullerenes) with biological objects is considered in sufficient detail. The article discusses the problem of receptor saturation and the activity of ex-orphan receptors that can act as targets for potential drugs. The prospects of creating new drugs based on π-cation interactions are shown. It was concluded that the study of the interaction of the substance and the receptor will allow to reveal the true mechanisms of dysregulatory pathology.

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“…Other recent reports show variable expression of CALCR mRNA with expression in only a subset 12/42 [26] or 115/152 [27] of primary tumours. In addition, Pal et al [28] report a correlation between patient survival and non-synonymous mutations in CTR.…”

Section: Introductionmentioning

confidence: 99%

Expression and activity of the calcitonin receptor family in a sample of primary human high-grade gliomas

et al. 2019

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Background Glioblastoma (GBM) is the most common and aggressive type of primary brain cancer. With median survival of less than 15 months, identification and validation of new GBM therapeutic targets is of critical importance. Results In this study we tested expression and performed pharmacological characterization of the calcitonin receptor (CTR) as well as other members of the calcitonin family of receptors in high-grade glioma (HGG) cell lines derived from individual patient tumours, cultured in defined conditions. Previous immunohistochemical data demonstrated CTR expression in GBM biopsies and we were able to confirm CALCR (gene encoding CTR) expression. However, as assessed by cAMP accumulation assay, only one of the studied cell lines expressed functional CTR, while the other cell lines have functional CGRP (CLR/RAMP1) receptors. The only CTR-expressing cell line (SB2b) showed modest coupling to the cAMP pathway and no activation of other known CTR signaling pathways, including ERK 1/2 and p38 MAP kinases, and Ca 2+ mobilization, supportive of low cell surface receptor expression. Exome sequencing data failed to account for the discrepancy between functional data and expression on the cell lines that do not respond to calcitonin(s) with no deleterious non-synonymous polymorphisms detected, suggesting that other factors may be at play, such as alternative splicing or rapid constitutive receptor internalisation. Conclusions This study shows that GPCR signaling can display significant variation depending on cellular system used, and effects seen in model recombinant cell lines or tumour cell lines are not always reproduced in a more physiologically relevant system and vice versa. Electronic supplementary material The online version of this article (10.1186/s12885-019-5369-y) contains supplementary material, which is available to authorized users.

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Loss-of-Function Mutations in Calcitonin Receptor (CALCR) Identify Highly Aggressive Glioblastoma with Poor Outcome

Cited by 24 publications

References 35 publications

Identification of hub genes and pathways in glioblastoma by bioinformatics analysis

Identification of hub genes and pathways in glioblastoma by bioinformatics analysis

Breach of ligand-receptor interaction in pathogenesis of disadaptive disorders and in pathology

Expression and activity of the calcitonin receptor family in a sample of primary human high-grade gliomas

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