The landscape of cancer-rewired GPCR signaling axes.

IF 11.1 Q1 CELL BIOLOGY
Chakit Arora, Marin Matic, Luisa Bisceglia, Pierluigi Di Chiaro, Natalia De Oliveira Rosa, Francesco Carli, Lauren Clubb, Lorenzo Amir Nemati Fard, Giorgos Kargas, Giuseppe R Diaferia, Ranka Vukotic, Luana Licata, Guanming Wu, Gioacchino Natoli, J Silvio Gutkind, Francesco Raimondi
{"title":"The landscape of cancer-rewired GPCR signaling axes.","authors":"Chakit Arora, Marin Matic, Luisa Bisceglia, Pierluigi Di Chiaro, Natalia De Oliveira Rosa, Francesco Carli, Lauren Clubb, Lorenzo Amir Nemati Fard, Giorgos Kargas, Giuseppe R Diaferia, Ranka Vukotic, Luana Licata, Guanming Wu, Gioacchino Natoli, J Silvio Gutkind, Francesco Raimondi","doi":"10.1016/j.xgen.2024.100557","DOIUrl":null,"url":null,"abstract":"<p><p>We explored the dysregulation of G-protein-coupled receptor (GPCR) ligand systems in cancer transcriptomics datasets to uncover new therapeutics opportunities in oncology. We derived an interaction network of receptors with ligands and their biosynthetic enzymes. Multiple GPCRs are differentially regulated together with their upstream partners across cancer subtypes and are associated to specific transcriptional programs and to patient survival patterns. The expression of both receptor-ligand (or enzymes) partners improved patient stratification, suggesting a synergistic role for the activation of GPCR networks in modulating cancer phenotypes. Remarkably, we identified many such axes across several cancer molecular subtypes, including many involving receptor-biosynthetic enzymes for neurotransmitters. We found that GPCRs from these actionable axes, including, e.g., muscarinic, adenosine, 5-hydroxytryptamine, and chemokine receptors, are the targets of multiple drugs displaying anti-growth effects in large-scale, cancer cell drug screens, which we further validated. We have made the results generated in this study freely available through a webapp (gpcrcanceraxes.bioinfolab.sns.it).</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":"4 5","pages":"100557"},"PeriodicalIF":11.1000,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11099383/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell genomics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.xgen.2024.100557","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

We explored the dysregulation of G-protein-coupled receptor (GPCR) ligand systems in cancer transcriptomics datasets to uncover new therapeutics opportunities in oncology. We derived an interaction network of receptors with ligands and their biosynthetic enzymes. Multiple GPCRs are differentially regulated together with their upstream partners across cancer subtypes and are associated to specific transcriptional programs and to patient survival patterns. The expression of both receptor-ligand (or enzymes) partners improved patient stratification, suggesting a synergistic role for the activation of GPCR networks in modulating cancer phenotypes. Remarkably, we identified many such axes across several cancer molecular subtypes, including many involving receptor-biosynthetic enzymes for neurotransmitters. We found that GPCRs from these actionable axes, including, e.g., muscarinic, adenosine, 5-hydroxytryptamine, and chemokine receptors, are the targets of multiple drugs displaying anti-growth effects in large-scale, cancer cell drug screens, which we further validated. We have made the results generated in this study freely available through a webapp (gpcrcanceraxes.bioinfolab.sns.it).

癌症重构的 GPCR 信号轴。
我们探索了癌症转录组学数据集中 G 蛋白偶联受体(GPCR)配体系统的失调,以发现肿瘤学中新的治疗机会。我们得出了受体与配体及其生物合成酶的相互作用网络。在不同的癌症亚型中,多种 GPCR 与其上游伙伴一起受到不同的调控,并与特定的转录程序和患者生存模式相关联。受体配体(或酶)伙伴的表达改善了患者分层,这表明 GPCR 网络的激活在调节癌症表型方面发挥着协同作用。值得注意的是,我们在几种癌症分子亚型中发现了许多这样的轴,包括许多涉及神经递质受体生物合成酶的轴。我们发现,在大规模癌细胞药物筛选中,来自这些可作用轴的 GPCR(包括毒蕈碱、腺苷、5-羟色胺和趋化因子受体等)是多种药物的靶点,这些药物具有抗生长作用,我们对这些靶点进行了进一步验证。我们通过一个网络应用程序(gpcrcanceraxes.bioinfolab.sns.it)免费提供了这项研究产生的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
7.10
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信