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Open AccessArticle

Comprehensive Map of the Regulated Cell Death Signaling Network: A Powerful Analytical Tool for Studying Diseases

1
Institut Curie, PSL Research University, Mines Paris Tech, Inserm, U900, 75005 Paris, France
2
Laboratoire de génétique médicale, CHRU-Nancy, F-54000 Nancy, France
3
Inserm, NGERE, Université de Lorraine, F-54000 Nancy, France
4
Centre de Recherches Interdisciplinaires, Université Paris Descartes, 75006 Paris, France
5
Faculty of Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia
6
Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177 Stockholm, Sweden
7
Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, 75006 Paris, France
8
Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France
9
Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France
10
Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou 215163, China
11
Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital, 171 77 Stockholm, Sweden
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(4), 990; https://doi.org/10.3390/cancers12040990
Received: 27 February 2020 / Accepted: 10 March 2020 / Published: 17 April 2020
(This article belongs to the Special Issue Cancer Modeling and Network Biology)
The processes leading to, or avoiding cell death are widely studied, because of their frequent perturbation in various diseases. Cell death occurs in three highly interconnected steps: Initiation, signaling and execution. We used a systems biology approach to gather information about all known modes of regulated cell death (RCD). Based on the experimental data retrieved from literature by manual curation, we graphically depicted the biological processes involved in RCD in the form of a seamless comprehensive signaling network map. The molecular mechanisms of each RCD mode are represented in detail. The RCD network map is divided into 26 functional modules that can be visualized contextually in the whole seamless network, as well as in individual diagrams. The resource is freely available and accessible via several web platforms for map navigation, data integration, and analysis. The RCD network map was employed for interpreting the functional differences in cell death regulation between Alzheimer’s disease and non-small cell lung cancer based on gene expression data that allowed emphasizing the molecular mechanisms underlying the inverse comorbidity between the two pathologies. In addition, the map was used for the analysis of genomic and transcriptomic data from ovarian cancer patients that provided RCD map-based signatures of four distinct tumor subtypes and highlighted the difference in regulations of cell death molecular mechanisms. View Full-Text
Keywords: regulated cell death; survival; signaling network; comprehensive map; biocuration; data visualization; module activity; lung cancer; Alzheimer’s disease; NaviCell regulated cell death; survival; signaling network; comprehensive map; biocuration; data visualization; module activity; lung cancer; Alzheimer’s disease; NaviCell
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MDPI and ACS Style

Ravel, J.-M.; Monraz Gomez, L.C.; Sompairac, N.; Calzone, L.; Zhivotovsky, B.; Kroemer, G.; Barillot, E.; Zinovyev, A.; Kuperstein, I. Comprehensive Map of the Regulated Cell Death Signaling Network: A Powerful Analytical Tool for Studying Diseases. Cancers 2020, 12, 990. https://doi.org/10.3390/cancers12040990

AMA Style

Ravel J-M, Monraz Gomez LC, Sompairac N, Calzone L, Zhivotovsky B, Kroemer G, Barillot E, Zinovyev A, Kuperstein I. Comprehensive Map of the Regulated Cell Death Signaling Network: A Powerful Analytical Tool for Studying Diseases. Cancers. 2020; 12(4):990. https://doi.org/10.3390/cancers12040990

Chicago/Turabian Style

Ravel, Jean-Marie; Monraz Gomez, L. C.; Sompairac, Nicolas; Calzone, Laurence; Zhivotovsky, Boris; Kroemer, Guido; Barillot, Emmanuel; Zinovyev, Andrei; Kuperstein, Inna. 2020. "Comprehensive Map of the Regulated Cell Death Signaling Network: A Powerful Analytical Tool for Studying Diseases" Cancers 12, no. 4: 990. https://doi.org/10.3390/cancers12040990

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