Journal
CANCERS
Volume 12, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/cancers12040990
Keywords
regulated cell death; survival; signaling network; comprehensive map; biocuration; data visualization; module activity; lung cancer; Alzheimer's disease; NaviCell
Categories
Funding
- APO-SYS EU
- INSERM Plan Cancer N COMET grant under ITMO Cancer BioSys program [BIO2014-08]
- Agence Nationale de la Recherche in the program Investissements d'Avenir [ANR-19-P3IA-0001]
- European Union [826121]
- CNRS [ANR-15-CMED-0001-04]
- HTE Inserm/ITMO Cancer program
- Ligue contre le Cancer (equipe labellisee)
- Agence National de la Recherche (ANR)-Projets blancs
- ANR
- ERA-Net for Research on Rare Diseases
- Association pour la recherche sur le cancer (ARC)
- Canceropole Ile-de-France
- European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR)
- Gustave Roussy Odyssea
- Fondation Carrefour
- High-end Foreign Expert Program in China [GDW20171100085, GDW20181100051]
- Institut National du Cancer (INCa)
- Institut Universitaire de France
- LeDucq Foundation
- LabEx Immuno-Oncology
- Seerave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumour Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
- Russian Science Foundation [19-15-00125, 190345, 181301]
- Chancelerie des universites de Paris (Legs Poix), Fondation pour la Recherche Medicale (FRM)
- European Union
- RHU Torino Lumiere
- Agence Nationale de la Recherche (ANR) [ANR-15-CMED-0001] Funding Source: Agence Nationale de la Recherche (ANR)
- Russian Science Foundation [19-15-00125] Funding Source: Russian Science Foundation
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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.
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