A comprehensive modular map of molecular interactions in RB/E2F pathway

Calzone, Laurence; Gelay, Amélie; Zinovyev, Andrei; Radvanyi, François; Barillot, Emmanuel

doi:10.1038/msb.2008.7

Cited by 119 publications

(107 citation statements)

References 70 publications

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“…Among E2F transcription factors, E2F1 is the only specific inducer of apoptosis that can target p53 in a reciprocal self-regulation of RB/E2F pathway. 41 AR can regulate the cell cycle-dependent transcription in prostate cancer cells by directly interacting with E2F1, 42 whereas E2F1 can deregulate androgen-dependent growth and enhance apoptosis in LNCaP. 43 By binding to RB1 in a cell cycle-dependent manner, E2F1 can specifically mediate the p53-dependent cell proliferation and apoptosis via upregulation of ASPP2.…”

Section: Discussionmentioning

confidence: 99%

Annexin‐A7 protects normal prostate cells and induces distinct patterns of RB‐associated cytotoxicity in androgen‐sensitive and ‐resistant prostate cancer cells

Torosyan

Šimáková

Shanmugam

et al. 2009

Intl Journal of Cancer

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The tumor suppressor role of annexin-A7 (ANXA7) was previously demonstrated by cancer susceptibility in Anxa7(1/2)-mice and by ANXA7 loss in human cancers, especially in hormone-resistant prostate tumors. To gain mechanistic insights into ANXA7 tumor suppression, we undertook an in vitro study in which we compared wild-type (WT)-ANXA7 and dominant-negative (DN)-ANXA7 effects to a conventional tumor suppressor p53 in prostate cancer cells with different androgen sensitivity. Unlike p53 (which caused cell growth arrest and apoptosis to a noticeable extent in benign PrEC), WT-ANXA7 demonstrated profound cytotoxicity in androgen-sensitive LNCaP as well as in the androgen-resistant DU145 and PC3 prostate cancer cells, but not in PrEC. In androgen-sensitive LNCaP, WT-ANXA7 decreased lowmolecular-weight (LMW) AR protein forms and maintained higher retinoblastoma 1 (RB1)/phospho-RB1 ratio. In contrast, DN-ANXA7 (which lacks phosphatidylserine liposome aggregation properties) increased LMW-AR forms and hyperphosphorylated RB1 that was consistent with the lack of DN-ANXA7 cytotoxicity. According to the microarray-based Ingenuity Pathways Analysis, a major WT-ANXA7 effect in androgen-sensitive LNCaP constituted of upregulation of the RB1-binding transcription factor E2F1 along with its downstream proapoptotic targets such as ASK1 and ASPP2. These results suggested a reversal of the RBdependent repression of the proapoptotic E2F-mediated transcription. However, DN-ANXA7 increased RB1/2 (but not E2F1) expression and induced the proliferation-promoting ERK5, thereby maintaining the RB-dependent repression of E2F-mediated apoptosis in LNcaP. On the other hand, in androgen-resistant cells, WT-ANXA7 tumor suppressor effects involved PTEN and NFkB pathways. Thus, ANXA7 revived the RB-associated cell survival control and overcame androgen resistance and dysfunctional status of major tumor suppressors commonly mutated in prostate cancer. Published 2009 UICC. This article is a US Government work and, as such, is in the public domain in the United States of America.Key words: annexin-A7 vs. p53; RB-E2F; AR; prostate cancer; Ingenuity Pathways Analysis Annexin-VII (ANXA7 or synexin) is a ubiquitously expressed member of the multifunctional Ca/phospholipid-binding annexin family. In addition to Ca 21 -activated GTPase activity as well as involvement in membrane fusion and exocytosis, ANXA7 demonstrated tumor suppressor function in murine model 1 and in human prostate and breast cancers. 2,3 Our large-scale study on ANXA7 protein expression in different cancers 4 identified a drastic ANXA7 loss in the hormone-refractory prostate cancers as well as an abundant ANXA7 presence in the adrenal gland, a major source of sex hormone precursors. Although tumor suppressor mechanisms of ANXA7 are not yet elucidated, these data suggested that ANXA7, which has androgen-receptor (AR) regulatory elements in its promoter, may be involved in the regulation of androgen-dependent cell survival in prostate cancer cells.Androgen-dependent proliferation is p...

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Section: Discussionmentioning

confidence: 99%

Annexin‐A7 protects normal prostate cells and induces distinct patterns of RB‐associated cytotoxicity in androgen‐sensitive and ‐resistant prostate cancer cells

Torosyan

Šimáková

Shanmugam

et al. 2009

Intl Journal of Cancer

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“…The syntax of this BiNoM Reaction Format (BRF) language have been depicted in [19,23] and in the BiNoM manual (https://binom.curie.fr/docs/BiNoM_Manual_v2.pdf).…”

Section: Brca1@cytoplasm -/> Brca1@nucleus Brca1@nucleus+bard1@nucleumentioning

confidence: 99%

“…This methodology served for creating the maps for ACSN resource [9]. The approach was also successfully applied in several studies [19,20]. Each step of the workflow starts from the problem statement and description of the principles, followed by a solution suggestion demonstrated on a typical example.…”

Section: Introductionmentioning

confidence: 99%

Signalling maps in cancer research: construction and data analysis

Kondratova

Sompairac

Barillot

et al. 2016

Preprint

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Graphical representation of molecular biology knowledge in the form of interactive diagrams became widely used in molecular and computational biology. It enables the scientific community to exchange and discuss information on cellular processes described in numerous scientific publications and to interpret high-throughput data. Constructing a signaling network map is a laborious process, therefore application of consistent procedures for representation of molecular processes and accurately organized annotation is essential for generation of a high-quality signaling network map that can be used by various computational tools. We summarize here the major aims and challenges of assembling information in a form of comprehensive maps of molecular interactions and suggest an optimized workflow. We share our experience gained while creating a biological network resource Atlas of Cancer Signaling Network (ACSN) that was successfully applied in several studies. We explain the map construction process. Then we address the problem of user interaction with large signaling maps and suggest to facilitate navigation by hierarchical organization of map structure and by application of semantic zooming principles. In addition, we describe a computational technology using Google Maps API to explore signaling networks in the manner similar to global geographical maps and provide the outline for preparing a biological network for this type of navigation. Nowadays the most demanded application of signaling maps is integration and functional interpretation of highthroughput data. We demonstrate several examples of cancer data visualization in the context of comprehensive signaling network maps.

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“…It is very well established that the active molecules of a living system such as DNA, RNAs, enzymes, receptor, hormones, metabolites, ions, etc., setup is essential for an integrated network to modulate the behavior of metabolic pathways (Autiero et al 2009). Several In silico comprehensive maps (Oda et al 2005;Kaizu et al 2010;Caron et al 2010;Oda and Kitano 2006;Wu et al 2010;Calzone et al 2008) have been developed for disease physiology, dynamic analysis, control mechanism, regulatory element detection for regulation/deregulation, and identification of biomarker for therapy of particular diseases.…”

Section: Introductionmentioning

confidence: 99%

Modeling and simulation analysis of propyl-thiouracil (PTU), an anti-thyroid drug on thyroid peroxidase (TPO), thyroid stimulating hormone receptor (TSHR), and sodium iodide (NIS) symporter based on systems biology approach

Gupta

Misra

2013

Netw Model Anal Health Inform Bioinforma

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The aim of metabolic modeling was to understand the cause effect interaction and reliance linked with the complex interactions of biological networks and molecular systems. Drugs that therapeutically modulate the biological processes of disease are often developed with limited knowledge of the underlying complexity of their specific targets. The robustness for systemic modulating behavior of thyroid hormone secretion during the course of different time unit simulation is explained in this study. In this work, a computational model has been developed which mimics the in vivo simulation. The model was constructed with the help of cell designer 4.1 used for analyzing the effect of perturbed amount of drugs at 0.1, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 amounts as a unit, targeting Thyroid Peroxidase (TPO), Thyroid Stimulating Hormone Receptor (TSHR), and Sodium Iodide Symporter (NIS). The rate kinetic equations were defined with each reaction to simulate the molecular species dynamic behavior. The modulating behavior of thyroid hormone secretion was analyzed by the process of activation and inactivation states of TPO, TSHR, and NIS at various amounts of drugs.Obtained results explain suitably the entire observable fact of the drug effects and are capable to proceed in response to the perturbations of the natural cell. TSHR was found as the most potent molecular therapeutic target in this study.

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A comprehensive modular map of molecular interactions in RB/E2F pathway

Cited by 119 publications

References 70 publications

Annexin‐A7 protects normal prostate cells and induces distinct patterns of RB‐associated cytotoxicity in androgen‐sensitive and ‐resistant prostate cancer cells

Annexin‐A7 protects normal prostate cells and induces distinct patterns of RB‐associated cytotoxicity in androgen‐sensitive and ‐resistant prostate cancer cells

Signalling maps in cancer research: construction and data analysis

Modeling and simulation analysis of propyl-thiouracil (PTU), an anti-thyroid drug on thyroid peroxidase (TPO), thyroid stimulating hormone receptor (TSHR), and sodium iodide (NIS) symporter based on systems biology approach

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