Expression of G Protein-Coupled Receptor 19 in Human Lung Cancer Cells Is Triggered by Entry into S-Phase and Supports G2–M Cell-Cycle Progression

Kastner, Stefan; Voss, Tilman; Keuerleber, Simon; Glöckel, Christina; Freissmuth, Michael; Sommergruber, Wolfgang

doi:10.1158/1541-7786.mcr-12-0139

Cited by 48 publications

(40 citation statements)

References 60 publications

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“…A number of genes are involved in cell-cycle processes, such as GPR19 , CDKN2A , USP11 and MX2 . GPR19 encodes for a G protein-coupled receptor and is reported to be associated with lung cancer and melanoma22. It is suggested that G protein-coupled receptors are the most “druggable” family of proteins23.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of gene expression studies in endometrial cancer identifies gene expression profiles associated with aggressive disease and patient outcome

O’Mara

Zhao

Spurdle

2016

Sci Rep

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Although endometrioid endometrial cancer (EEC; comprising ~80% of all endometrial cancers diagnosed) is typically associated with favourable patient outcome, a significant portion (~20%) of women with this subtype will relapse. We hypothesised that gene expression predictors of the more aggressive non-endometrioid endometrial cancers (NEEC) could be used to predict EEC patients with poor prognosis. To explore this hypothesis, we performed meta-analysis of 12 gene expression microarray studies followed by validation using RNA-Seq data from The Cancer Genome Atlas (TCGA) and identified 1,253 genes differentially expressed between EEC and NEEC. Analysis found 121 genes were associated with poor outcome among EEC patients. Forward selection likelihood-based modelling identified a 9-gene signature associated with EEC outcome in our discovery RNA-Seq dataset which remained significant after adjustment for clinical covariates, but was not significant in a smaller RNA-Seq dataset. Our study demonstrates the value of employing meta-analysis to improve the power of gene expression microarray data, and highlight genes and molecular pathways of importance for endometrial cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Meta-analysis of gene expression studies in endometrial cancer identifies gene expression profiles associated with aggressive disease and patient outcome

O’Mara

Zhao

Spurdle

2016

Sci Rep

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“…); moreover, expression of GPR19 in lung cancer cells is triggered by entry into S‐phase and in this case seems to promote progression from G2 to M phase (Kastner et al. ).…”

Section: Discussionmentioning

confidence: 99%

“…This is interesting not least because the situation appears to be different for some other GPCRs that exhibit cell-cycle dependent regulation of expression. For example the chemokine receptor CXCR3 is expressed in both S and G2-M phases in human microvascular endothelial cells (Romagnani et al 2001); moreover, expression of GPR19 in lung cancer cells is triggered by entry into S-phase and in this case seems to promote progression from G2 to M phase (Kastner et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration

et al. 2017

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The well‐known action of the gastric hormone gastrin in stimulating gastric acid secretion is mediated by activation of cholecystokinin‐2 receptors (CCK2R). The latter are expressed by a variety of cell types suggesting that gastrin is implicated in multiple functions. During wound healing in the stomach CCK2R may be expressed by myofibroblasts. We have now characterized CCK2R expression in cultured myofibroblasts. Immunocytochemistry showed that a relatively small proportion (1–6%) of myofibroblasts expressed the receptor regardless of the region of the gut from which they were derived, or whether from cancer or control tissue. Activation of CCK2R by human heptadecapeptide gastrin (hG17) increased intracellular calcium concentrations in a small subset of myofibroblasts indicating the presence of a functional receptor. Unexpectedly, we found over 80% of cells expressing CCK2R were also labeled with 5‐ethynyl‐2′‐deoxyuridine (EdU) which is incorporated into DNA during S‐phase of the cell cycle. hG17 did not stimulate EdU incorporation but increased migration of both EdU‐labeled and unlabelled myofibroblasts; the migratory response was inhibited by a CCK2R antagonist and by an inhibitor of IGF receptor tyrosine kinase; hG17 also increased IGF‐2 transcript abundance. The data suggest myofibroblasts express CCK2R in a restricted period of the cell cycle during S‐phase, and that gastrin accelerates migration of these cells; it also stimulates migration of adjacent cells probably through paracrine release of IGF. Together with previous findings, the results raise the prospect that gastrin controls the position of dividing myofibroblasts which may be relevant in wound healing and cancer progression in the gastrointestinal tract.

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“…The gene expression profiling in Kastner et al's work was used in our study [13], which includes 8 SCLC, 16 NSCLC, and 14 normal lung tissue samples. It was retrieved from NCBI Gene Expression Omnibus (GEO) (Accession number: GSE40275).…”

Section: Methodsmentioning

confidence: 99%

Identification of Lung-Cancer-Related Genes with the Shortest Path Approach in a Protein-Protein Interaction Network

You

Lei

et al. 2013

BioMed Research International

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Lung cancer is one of the leading causes of cancer mortality worldwide. The main types of lung cancer are small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC). In this work, a computational method was proposed for identifying lung-cancer-related genes with a shortest path approach in a protein-protein interaction (PPI) network. Based on the PPI data from STRING, a weighted PPI network was constructed. 54 NSCLC- and 84 SCLC-related genes were retrieved from associated KEGG pathways. Then the shortest paths between each pair of these 54 NSCLC genes and 84 SCLC genes were obtained with Dijkstra's algorithm. Finally, all the genes on the shortest paths were extracted, and 25 and 38 shortest genes with a permutation P value less than 0.05 for NSCLC and SCLC were selected for further analysis. Some of the shortest path genes have been reported to be related to lung cancer. Intriguingly, the candidate genes we identified from the PPI network contained more cancer genes than those identified from the gene expression profiles. Furthermore, these genes possessed more functional similarity with the known cancer genes than those identified from the gene expression profiles. This study proved the efficiency of the proposed method and showed promising results.

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Expression of G Protein-Coupled Receptor 19 in Human Lung Cancer Cells Is Triggered by Entry into S-Phase and Supports G2–M Cell-Cycle Progression

Cited by 48 publications

References 60 publications

Meta-analysis of gene expression studies in endometrial cancer identifies gene expression profiles associated with aggressive disease and patient outcome

Meta-analysis of gene expression studies in endometrial cancer identifies gene expression profiles associated with aggressive disease and patient outcome

Cell cycle dependent expression of the CCK2 receptor by gastrointestinal myofibroblasts: putative role in determining cell migration

Identification of Lung-Cancer-Related Genes with the Shortest Path Approach in a Protein-Protein Interaction Network

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