{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T13:20:35Z","timestamp":1781702435891,"version":"3.54.5"},"reference-count":155,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T00:00:00Z","timestamp":1446508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1004571","type":"journal-article","created":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T19:00:30Z","timestamp":1446577230000},"page":"e1004571","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":124,"title":["Mathematical Modelling of Molecular Pathways Enabling Tumour Cell Invasion and Migration"],"prefix":"10.1371","volume":"11","author":[{"given":"David P. A.","family":"Cohen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loredana","family":"Martignetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Robine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Barillot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei","family":"Zinovyev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Calzone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2015,11,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.3322\/caac.20121","article-title":"Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths","volume":"61","author":"R Siegel","journal-title":"CA Cancer J Clin"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/nrc3628","article-title":"Crossing the endothelial barrier during metastasis","volume":"13","author":"N Reymond","year":"2013","journal-title":"Nat Rev Cancer"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.mrrev.2011.05.002","article-title":"Initial steps of metastasis: cell invasion and endothelial transmigration","volume":"728","author":"F Van Zijl","year":"2011","journal-title":"Mutat Res"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/ng1060","article-title":"A molecular signature of metastasis in primary solid tumors","volume":"33","author":"S Ramaswamy","year":"2003","journal-title":"Nat Genet"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1126\/science.1161621","article-title":"Seeding and propagation of untransformed mouse mammary cells in the lung","volume":"321","author":"K Podsypanina","year":"2008","journal-title":"Science"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.2217\/fon.13.101","article-title":"Circulating tumor cells: utopia or reality?","volume":"9","author":"V Conteduca","year":"2013","journal-title":"Future Oncol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-mesenchymal transitions in development and disease","volume":"139","author":"JP Thiery","year":"2009","journal-title":"Cell"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.ctrv.2011.11.001","article-title":"Epithelial-mesenchymal transition and breast cancer: Role, molecular mechanisms and clinical impact","volume":"38","author":"C Foroni","year":"2012","journal-title":"Cancer Treat Rev"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1172\/JCI39104","article-title":"The basics of epithelial-mesenchymal transition","volume":"119","author":"R Kalluri","year":"2009","journal-title":"J Clin Invest"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1172\/JCI36183","article-title":"Biomarkers for epithelial-mesenchymal transitions","volume":"119","author":"M Zeisberg","year":"2009","journal-title":"J Clin Invest"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"3429","DOI":"10.1007\/s00018-012-1122-2","article-title":"EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness","volume":"69","author":"E S\u00e1nchez-Till\u00f3","year":"2012","journal-title":"Cell Mol Life Sci"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1146\/annurev-cellbio-092910-154036","article-title":"The ins and outs of the epithelial to mesenchymal transition in health and disease","volume":"27","author":"MA Nieto","year":"2011","journal-title":"Annu Rev Cell Dev Biol"},{"key":"ref13","first-page":"293","article-title":"Metastasis mechanisms","volume":"1796","author":"TR Geiger","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrc2620","article-title":"Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits","volume":"9","author":"K Polyak","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrm1835","article-title":"Complex networks orchestrate epithelial-mesenchymal transitions","volume":"7","author":"JP Thiery","year":"2006","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/ncb1875","article-title":"p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug","volume":"11","author":"S-P Wang","year":"2009","journal-title":"Nat Cell Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/ng747","article-title":"Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer","volume":"29","author":"J Jonkers","year":"2001","journal-title":"Nat Genet"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1046\/j.1365-2168.2000.01513.x","article-title":"E-cadherin-catenin cell-cell adhesion complex and human cancer","volume":"87","author":"BP Wijnhoven","year":"2000","journal-title":"Br J Surg"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"365","DOI":"10.4161\/cam.21326","article-title":"The regulation of cell-cell adhesion during epithelial-mesenchymal transition, motility and tumor progression","volume":"6","author":"GF Le Bras","year":"2012","journal-title":"Cell Adh Migr"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.ceb.2011.12.004","article-title":"Directed cell invasion and migration during metastasis","volume":"24","author":"JJ Bravo-Cordero","year":"2012","journal-title":"Curr Opin Cell Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1038\/nm.3391","article-title":"Tumor metastasis: moving new biological insights into the clinic","volume":"19","author":"L Wan","year":"2013","journal-title":"Nat Med"},{"key":"ref22","first-page":"29","article-title":"New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers: outside-in signaling and relationship to tumor progression","volume":"1825","author":"B Bauvois","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"ref23","first-page":"461","article-title":"Computational Systems Biology of Cancer","author":"E Barillot","year":"2012"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.cell.2006.09.042","article-title":"Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment","volume":"127","author":"ARA Anderson","year":"2006","journal-title":"Cell"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.jtbi.2010.08.028","article-title":"Tumour-stromal interactions in acid-mediated invasion: a mathematical model","volume":"267","author":"NK Martin","year":"2010","journal-title":"J Theor Biol"},{"key":"ref26","article-title":"Mathematical model of macrophage-facilitated breast cancer cells invasion","author":"H Knutsdottir","year":"2014","journal-title":"J Theor Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"18144","DOI":"10.1073\/pnas.1318192110","article-title":"MicroRNA-based regulation of epithelial-hybrid-mesenchymal fate determination","volume":"110","author":"M Lu","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.bpj.2013.07.011","article-title":"Coupled reversible and irreversible bistable switches underlying TGF\u03b2-induced epithelial to mesenchymal transition","volume":"105","author":"X-J Tian","year":"2013","journal-title":"Biophys J"},{"key":"ref29","article-title":"TGF-\u03b2-induced epithelial-to-mesenchymal transition proceeds through stepwise activation of multiple feedback loops","author":"J Zhang","year":"2014","journal-title":"Sci Signal 7: ra91"},{"key":"ref30","first-page":"90","article-title":"Molecular signature of epithelial-mesenchymal transition (EMT) in human prostate cancer bone metastasis","volume":"3","author":"S Sethi","year":"2010","journal-title":"Am J Transl Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.1038\/ncomms6005","article-title":"Concomitant Notch activation and p53 deletion trigger epithelial-to-mesenchymal transition and metastasis in mouse gut","volume":"5","author":"M Chanrion","year":"2014","journal-title":"Nat Commun"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1101\/gad.225334.113","article-title":"Epithelial-mesenchymal plasticity in carcinoma metastasis","volume":"27","author":"JH Tsai","year":"2013","journal-title":"Genes Dev"},{"key":"ref33","unstructured":"Signaling network of EMT regulation <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/navicell.curie.fr\/navicell\/maps\/signallingnetworkofemtregulation\/master\/index.html\" xlink:type=\"simple\">http:\/\/navicell.curie.fr\/navicell\/maps\/signallingnetworkofemtregulation\/master\/index.html<\/ext-link>"},{"key":"ref34","first-page":"306879","article-title":"Anoikis resistance: an essential prerequisite for tumor metastasis","volume":"2012","author":"Y-N Kim","year":"2012","journal-title":"Int J Cell Biol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nature04296","article-title":"Oncogenic pathway signatures in human cancers as a guide to targeted therapies","volume":"439","author":"AH Bild","year":"2006","journal-title":"Nature"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"D277","DOI":"10.1093\/nar\/gkh063","article-title":"The KEGG resource for deciphering the genome","volume":"32","author":"M Kanehisa","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nature11252","article-title":"Comprehensive molecular characterization of human colon and rectal cancer","volume":"487","year":"2012","journal-title":"Nature"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1093\/bioinformatics\/btp683","article-title":"ConceptGen: a gene set enrichment and gene set relation mapping tool","volume":"26","author":"MA Sartor","year":"2010","journal-title":"Bioinformatics"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/1752-0509-3-73","article-title":"An integrative ChIP-chip and gene expression profiling to model SMAD regulatory modules","volume":"3","author":"H Qin","year":"2009","journal-title":"BMC Syst Biol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1093\/bioinformatics\/btq124","article-title":"BoolNet\u2014an R package for generation, reconstruction and analysis of Boolean networks","volume":"26","author":"C M\u00fcssel","year":"2010","journal-title":"Bioinformatics"},{"key":"ref42","first-page":"340","article-title":"Principal Manifolds for Data Visualisation and Dimension Reduction","volume":"Vol. 58","author":"A Gorban","year":"2008"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1142\/S0129065710002383","article-title":"Principal manifolds and graphs in practice: from molecular biology to dynamical systems","volume":"20","author":"AN Gorban","year":"2010","journal-title":"Int J Neural Syst"},{"key":"ref44","unstructured":"Gorban A., Pitenko A., Zinovyev A (2014) ViDaExpert: user-friendly tool for nonlinear visualization and analysis of multidimensional vectorial data. URL: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/arxiv.org\/abs\/1406.5550\" xlink:type=\"simple\">http:\/\/arxiv.org\/abs\/1406.5550<\/ext-link>"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1186\/bcr3037","article-title":"Breast cancer epithelial-to-mesenchymal transition: examining the functional consequences of plasticity","volume":"13","author":"DJ Drasin","year":"2011","journal-title":"Breast Cancer Res"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"9543","DOI":"10.1158\/0008-5472.CAN-06-0479","article-title":"Genetic profiling of epithelial cells expressing E-cadherin repressors reveals a distinct role for Snail, Slug, and E47 factors in epithelial-mesenchymal transition","volume":"66","author":"G Moreno-Bueno","year":"2006","journal-title":"Cancer Res"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1083\/jcb.200308162","article-title":"Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK","volume":"163","author":"M Conacci-Sorrell","year":"2003","journal-title":"J Cell Biol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.cell.2004.06.006","article-title":"Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis","volume":"117","author":"J Yang","year":"2004","journal-title":"Cell"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1242\/dev.007047","article-title":"Zeb1 links epithelial-mesenchymal transition and cellular senescence","volume":"135","author":"Y Liu","year":"2008","journal-title":"Development"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/S1097-2765(01)00260-X","article-title":"The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion","volume":"7","author":"J Comijn","year":"2001","journal-title":"Mol Cell"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1097\/CCO.0b013e32835b6371","article-title":"TGF-\u03b2 signaling and epithelial-mesenchymal transition in cancer progression","volume":"25","author":"Y Katsuno","year":"2013","journal-title":"Curr Opin Oncol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"e78200","DOI":"10.1371\/journal.pone.0078200","article-title":"The role of nuclear \u03b2-catenin accumulation in the Twist2-induced ovarian cancer EMT","volume":"8","author":"Y Mao","year":"2013","journal-title":"PLoS One"},{"key":"ref53","article-title":"Deadly crosstalk: Notch signaling at the intersection of EMT and cancer stem cells","author":"I Espinoza","year":"2013","journal-title":"Cancer Lett"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1101\/gad.276304","article-title":"Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation","volume":"18","author":"LA Timmerman","year":"2004","journal-title":"Genes Dev"},{"key":"ref55","first-page":"2172","article-title":"The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines","volume":"63","author":"SJ Grille","year":"2003","journal-title":"Cancer Res"},{"key":"ref56","article-title":"Activation of AKT signaling promotes epithelial-mesenchymal transition and tumor growth in colorectal cancer cells","author":"S Suman","year":"2013","journal-title":"Mol Carcinog"},{"key":"ref57","article-title":"ZEB\/miR-200 feedback loop: At the crossroads of signal transduction in cancer","author":"L Hill","year":"2012","journal-title":"Int J Cancer"},{"key":"ref58","article-title":"MiR-1 and miR-200 inhibit EMT via Slug-dependent and tumorigenesis via Slug-independent mechanisms","author":"Y-N Liu","year":"2012","journal-title":"Oncogene"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"e35440","DOI":"10.1371\/journal.pone.0035440","article-title":"A Novel Network Integrating a miRNA-203\/SNAI1 Feedback Loop which Regulates Epithelial to Mesenchymal Transition","volume":"7","author":"M Moes","year":"2012","journal-title":"PLoS One"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"4256","DOI":"10.4161\/cc.10.24.18552","article-title":"miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions","volume":"10","author":"H Siemens","year":"2011","journal-title":"Cell Cycle"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1111\/j.1365-2133.2012.10824.x","article-title":"Cadherin switch from E- to N-cadherin in melanoma progression is regulated by the PI3K\/PTEN pathway through Twist and Snail","volume":"166","author":"L Hao","year":"2012","journal-title":"Br J Dermatol"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"10644","DOI":"10.1128\/JVI.00703-10","article-title":"MicroRNA 203 expression in keratinocytes is dependent on regulation of p53 levels by E6","volume":"84","author":"DJ McKenna","year":"2010","journal-title":"J Virol"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.4161\/cc.6.13.4436","article-title":"Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest","volume":"6","author":"V Tarasov","year":"2007","journal-title":"Cell Cycle"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1083\/jcb.201103097","article-title":"A p53\/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition","volume":"195","author":"NH Kim","year":"2011","journal-title":"J Cell Biol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/nar\/gkr731","article-title":"An integrative genomic approach identifies p73 and p63 as activators of miR-200 microRNA family transcription","volume":"40","author":"EC Knouf","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1038\/jid.2009.438","article-title":"Transcriptional repression of miR-34 family contributes to p63-mediated cell cycle progression in epidermal cells","volume":"130","author":"D Antonini","year":"2010","journal-title":"J Invest Dermatol"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"21099","DOI":"10.1073\/pnas.1112063108","article-title":"microRNA-34a regulates neurite outgrowth, spinal morphology, and function","volume":"108","author":"M Agostini","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"5287","DOI":"10.1158\/1078-0432.CCR-10-2619","article-title":"Regulatory Role of mir-203 in Prostate Cancer Progression and Metastasis","volume":"17","author":"S Saini","year":"2011","journal-title":"Clin Cancer Res"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"886","DOI":"10.4161\/cc.3.7.996","article-title":"p73 and p63: why do we still need them?","volume":"3","author":"G Blandino","year":"2004","journal-title":"Cell Cycle"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"a004887","DOI":"10.1101\/cshperspect.a004887","article-title":"p63 and p73, the ancestors of p53","volume":"2","author":"V D\u00f6tsch","year":"2010","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/j.yexcr.2012.01.023","article-title":"p63\/p73 in the control of cell cycle and cell death","volume":"318","author":"N Allocati","year":"2012","journal-title":"Exp Cell Res"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/nrc2675","article-title":"Crosstalk of Notch with p53 and p63 in cancer growth control","volume":"9","author":"GP Dotto","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/cdd.2008.178","article-title":"Mitochondrial DNA depletion in prostate epithelial cells promotes anoikis resistance and invasion through activation of PI3K\/Akt2","volume":"16","author":"L Moro","year":"2009","journal-title":"Cell Death Differ"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.4161\/cc.10.21.18182","article-title":"Notch signaling mediates p63-induced quiescence: a new facet of p63\/Notch crosstalk","volume":"10","author":"N Forster","year":"2011","journal-title":"Cell Cycle"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"4584","DOI":"10.4161\/cc.9.22.13871","article-title":"Interaction of regulators Mdm2 and Mdmx with transcription factors p53, p63 and p73","volume":"9","author":"M Zdzalik","year":"2010","journal-title":"Cell Cycle"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.tcb.2010.03.004","article-title":"The regulation of energy metabolism and the IGF-1\/mTOR pathways by the p53 protein","volume":"20","author":"Z Feng","year":"2010","journal-title":"Trends Cell Biol"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.bbrc.2010.11.043","article-title":"MDM2 promotes the proteasomal degradation of p73 through the interaction with Itch in HeLa cells","volume":"403","author":"N Kubo","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1016\/j.bbamcr.2011.03.010","article-title":"Akt, FoxO and regulation of apoptosis","volume":"1813","author":"X Zhang","year":"2011","journal-title":"Biochim Biophys Acta"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"e10226","DOI":"10.1371\/journal.pone.0010226","article-title":"Activation of the Akt survival pathway contributes to TRAIL resistance in cancer cells","volume":"5","author":"J Xu","year":"2010","journal-title":"PLoS One"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"11352","DOI":"10.1074\/jbc.M109062200","article-title":"AKT\/PKB phosphorylation of p21Cip\/WAF1 enhances protein stability of p21Cip\/WAF1 and promotes cell survival","volume":"277","author":"Y Li","year":"2002","journal-title":"J Biol Chem"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"ra62","DOI":"10.1126\/scisignal.2000356","article-title":"MicroRNAs differentially regulated by Akt isoforms control EMT and stem cell renewal in cancer cells","volume":"2","author":"D Iliopoulos","year":"2009","journal-title":"Sci Signal"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.molcel.2010.02.031","article-title":"The actin-bundling protein palladin is an Akt1-specific substrate that regulates breast cancer cell migration","volume":"38","author":"YR Chin","year":"2010","journal-title":"Mol Cell"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"211","DOI":"10.4161\/cam.5.3.15790","article-title":"Akt isoform-specific signaling in breast cancer: uncovering an anti-migratory role for palladin","volume":"5","author":"YR Chin","year":"2011","journal-title":"Cell Adh Migr"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1073\/pnas.0511342103","article-title":"Mechanism of Akt1 inhibition of breast cancer cell invasion reveals a protumorigenic role for TSC2","volume":"103","author":"H Liu","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"8267","DOI":"10.1128\/MCB.00201-06","article-title":"Only Akt1 is required for proliferation, while Akt2 promotes cell cycle exit through p21 binding","volume":"26","author":"L H\u00e9ron-Milhavet","year":"2006","journal-title":"Mol Cell Biol"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"e76987","DOI":"10.1371\/journal.pone.0076987","article-title":"Characterization of the Akt2 domain essential for binding nuclear p21cip1 to promote cell cycle arrest during myogenic differentiation","volume":"8","author":"L Heron-Milhavet","year":"2013","journal-title":"PLoS One"},{"key":"ref87","first-page":"19","article-title":"Physiological regulation of Akt activity and stability","volume":"2","author":"Y Liao","year":"2010","journal-title":"Am J Transl Res"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/S0022-3565(24)29451-9","article-title":"Growth factor signaling in cell survival: implications for cancer treatment","volume":"298","author":"S Talapatra","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"18842","DOI":"10.1074\/jbc.M700243200","article-title":"A novel modulatory mechanism of transforming growth factor-beta signaling through decorin and LRP-1","volume":"282","author":"C Cabello-Verrugio","year":"2007","journal-title":"J Biol Chem"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"32634","DOI":"10.1016\/S0021-9258(18)31681-8","article-title":"Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity","volume":"269","author":"Y Takeuchi","year":"1994","journal-title":"J Biol Chem"},{"issue":"Pt 3","key":"ref91","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1042\/bj3370537","article-title":"Dermatopontin interacts with transforming growth factor beta and enhances its biological activity","volume":"337","author":"O Okamoto","year":"1999","journal-title":"Biochem J"},{"key":"ref92","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a011213","article-title":"Notch signaling","volume":"4","author":"R Kopan","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.2741\/2394","article-title":"Notch signaling and its role in breast cancer","volume":"12","author":"F Wu","year":"2007","journal-title":"Front Biosci"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.biosystems.2005.10.003","article-title":"GINsim: a software suite for the qualitative modelling, simulation and analysis of regulatory networks","volume":"84","author":"AG Gonzalez","year":"2006","journal-title":"Biosystems"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"e1155","DOI":"10.1038\/cddis.2014.122","article-title":"Downregulation of FAP suppresses cell proliferation and metastasis through PTEN\/PI3K\/AKT and Ras-ERK signaling in oral squamous cell carcinoma","volume":"5","author":"H Wang","year":"2014","journal-title":"Cell Death Dis"},{"key":"ref96","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3892\/ol.2011.487","article-title":"C-Src-mediated RANKL-induced breast cancer cell migration by activation of the ERK and Akt pathway","volume":"3","author":"L Zhang","year":"2012","journal-title":"Oncol Lett"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1161\/01.ATV.0000066132.32063.F2","article-title":"Role of JNK, p38, and ERK in platelet-derived growth factor-induced vascular proliferation, migration, and gene expression","volume":"23","author":"Y Zhan","year":"2003","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/ng.211","article-title":"Kras regulatory elements and exon 4A determine mutation specificity in lung cancer","volume":"40","author":"MD To","year":"2008","journal-title":"Nat Genet"},{"key":"ref99","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/ng721","article-title":"Wildtype Kras2 can inhibit lung carcinogenesis in mice","volume":"29","author":"Z Zhang","year":"2001","journal-title":"Nat Genet"},{"key":"ref100","doi-asserted-by":"crossref","first-page":"934","DOI":"10.3748\/wjg.v13.i6.934","article-title":"Growth inhibitory effect of wild-type Kras2 gene on a colonic adenocarcinoma cell line","volume":"13","author":"H Li","year":"2007","journal-title":"World J Gastroenterol"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1074\/jbc.M112.394130","article-title":"Identification of mutant K-Ras-dependent phenotypes using a panel of isogenic cell lines","volume":"288","author":"S Vartanian","year":"2013","journal-title":"J Biol Chem"},{"key":"ref102","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1002\/jcp.22969","article-title":"Wild type N-ras displays anti-malignant properties, in part by downregulating decorin","volume":"227","author":"M Benet","year":"2012","journal-title":"J Cell Physiol"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1158\/2159-8290.CD-13-0096","article-title":"Dominant role of oncogene dosage and absence of tumor suppressor activity in Nras-driven hematopoietic transformation","volume":"3","author":"J Xu","year":"2013","journal-title":"Cancer Discov"},{"key":"ref104","first-page":"326","article-title":"Functions and Regulation of the PTEN Gene in Colorectal Cancer","volume":"3","author":"F Molinari","year":"2013","journal-title":"Front Oncol"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1007\/s00018-011-0878-0","article-title":"Genetic alterations of PTEN in human melanoma","volume":"69","author":"A-H Aguissa-Tour\u00e9","year":"2012","journal-title":"Cell Mol Life Sci"},{"key":"ref106","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.2174\/138161211797249224","article-title":"Targeting the AKT pathway in glioblastoma","volume":"17","author":"KA McDowell","year":"2011","journal-title":"Curr Pharm Des"},{"key":"ref107","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.celrep.2014.01.030","article-title":"PTEN C-terminal deletion causes genomic instability and tumor development","volume":"6","author":"Z Sun","year":"2014","journal-title":"Cell Rep"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/mc.21903","article-title":"Attenuation of PTEN perturbs genomic stability via activation of Akt and down-regulation of Rad51 in human embryonic kidney cells","volume":"52","author":"A Mukherjee","year":"2013","journal-title":"Mol Carcinog"},{"key":"ref109","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.2353\/ajpath.2010.090931","article-title":"The critical role of AKT2 in hepatic steatosis induced by PTEN loss","volume":"176","author":"L He","year":"2010","journal-title":"Am J Pathol"},{"key":"ref110","first-page":"4175","article-title":"Diverse prognostic roles of Akt isoforms, PTEN and PI3K in tumor epithelial cells and stromal compartment in non-small cell lung cancer","volume":"29","author":"S Al-Saad","year":"2009","journal-title":"Anticancer Res"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature04809","article-title":"Identification of a tumour suppressor network opposing nuclear Akt function","volume":"441","author":"LC Trotman","year":"2006","journal-title":"Nature"},{"key":"ref112","article-title":"Pten-deficient tumors depend on akt2 for maintenance and survival","author":"YMR Chin","year":"2014","journal-title":"Cancer Discov"},{"key":"ref113","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1038\/leu.2011.103","article-title":"p53 and Notch signaling in chronic lymphocytic leukemia: clues to identifying novel therapeutic strategies","volume":"25","author":"RG Wickremasinghe","year":"2011","journal-title":"Leuk Off J Leuk Soc Am Leuk Res Fund, UK"},{"key":"ref114","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1093\/jb\/mvq114","article-title":"Autocrine TGF-\u03b2 protects breast cancer cells from apoptosis through reduction of BH3-only protein, Bim","volume":"149","author":"Y Hoshino","year":"2011","journal-title":"J Biochem"},{"key":"ref115","first-page":"197","article-title":"Sodium butyrate induces apoptosis of human colon cancer cells by modulating ERK and sphingosine kinase 2","volume":"27","author":"M Xiao","year":"2014","journal-title":"Biomed Environ Sci"},{"key":"ref116","doi-asserted-by":"crossref","first-page":"14884","DOI":"10.1073\/pnas.0902042106","article-title":"SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer","volume":"106","author":"AE Sayan","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref117","doi-asserted-by":"crossref","first-page":"3525","DOI":"10.1007\/s13277-013-1465-9","article-title":"The influence of AKT isoforms on radiation sensitivity and DNA repair in colon cancer cell lines","volume":"35","author":"SH Sahlberg","year":"2014","journal-title":"Tumour Biol"},{"key":"ref118","doi-asserted-by":"crossref","first-page":"567","DOI":"10.3892\/or.2012.1813","article-title":"TGF-\u03b2 autocrine pathway and MAPK signaling promote cell invasiveness and in vivo mammary adenocarcinoma tumor progression","volume":"28","author":"MC Daroqui","year":"2012","journal-title":"Oncol Rep"},{"key":"ref119","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1471-2407-12-26","article-title":"TGF-\u03b21 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1\/2 in highly invasive breast cancer cells","volume":"12","author":"LR Gomes","year":"2012","journal-title":"BMC Cancer"},{"key":"ref120","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.15252\/emmm.201404208","article-title":"Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients","volume":"6","author":"TZ Tan","year":"2014","journal-title":"EMBO Mol Med"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.3748\/wjg.v18.i21.2640","article-title":"Suppression of colorectal cancer metastasis by nigericin through inhibition of epithelial-mesenchymal transition","volume":"18","author":"H-M Zhou","year":"2012","journal-title":"World J Gastroenterol"},{"key":"ref122","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1091\/mbc.E11-04-0306","article-title":"Down-regulation of epithelial cadherin is required to initiate metastatic outgrowth of breast cancer","volume":"22","author":"MK Wendt","year":"2011","journal-title":"Mol Biol Cell"},{"key":"ref123","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/1752-0509-6-116","article-title":"Continuous time Boolean modeling for biological signaling: application of Gillespie algorithm","volume":"6","author":"G Stoll","year":"2012","journal-title":"BMC Syst Biol"},{"key":"ref124","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1083\/jcb.201009059","article-title":"p53 and its mutants in tumor cell migration and invasion","volume":"192","author":"PAJ Muller","year":"2011","journal-title":"J Cell Biol"},{"key":"ref125","first-page":"1598","article-title":"A possible role of p73 on the modulation of p53 level through MDM2","volume":"61","author":"XQ Wang","year":"2001","journal-title":"Cancer Res"},{"key":"ref126","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1158\/0008-5472.CAN-08-4312","article-title":"Acquisition of epithelial-mesenchymal transition phenotype of gemcitabine-resistant pancreatic cancer cells is linked with activation of the notch signaling pathway","volume":"69","author":"Z Wang","year":"2009","journal-title":"Cancer Res"},{"key":"ref127","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/nri3607","article-title":"Apoptotic cell clearance: basic biology and therapeutic potential","volume":"14","author":"IKH Poon","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"ref128","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1593\/neo.121828","article-title":"Down-regulation of the miRNA-200 family at the invasive front of colorectal cancers with degraded basement membrane indicates EMT is involved in cancer progression","volume":"15","author":"EL Paterson","year":"2013","journal-title":"Neoplasia"},{"key":"ref129","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/gene.20042","article-title":"Tissue-specific and inducible Cre-mediated recombination in the gut epithelium","volume":"39","author":"F El Marjou","year":"2004","journal-title":"Genesis"},{"key":"ref130","doi-asserted-by":"crossref","first-page":"14920","DOI":"10.1073\/pnas.2436557100","article-title":"Notch signaling controls multiple steps of pancreatic differentiation","volume":"100","author":"LC Murtaugh","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/1471-2164-15-74","article-title":"Comprehensive analysis of \u03b2-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt\/\u03b2-catenin signaling","volume":"15","author":"A Herbst","year":"2014","journal-title":"BMC Genomics"},{"key":"ref132","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2010.12.070","article-title":"WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer","volume":"406","author":"J Zeilstra","year":"2011","journal-title":"Biochem Biophys Res Commun"},{"key":"ref133","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.2174\/138945010792006780","article-title":"A Wnt-ow of opportunity: targeting the Wnt\/beta-catenin pathway in breast cancer","volume":"11","author":"JR Prosperi","year":"2010","journal-title":"Curr Drug Targets"},{"key":"ref134","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3109\/15419061.2011.636465","article-title":"E-cadherin and the cytoskeletal network in colorectal cancer development and metastasis","volume":"18","author":"A Buda","year":"2011","journal-title":"Cell Commun Adhes"},{"key":"ref135","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1016\/j.cellsig.2012.08.004","article-title":"PI3K\/Akt to GSK3\u03b2\/\u03b2-catenin signaling cascade coordinates cell colonization for bladder cancer bone metastasis through regulating ZEB1 transcription","volume":"24","author":"K Wu","year":"2012","journal-title":"Cell Signal"},{"key":"ref136","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4251\/wjgo.v2.i3.151","article-title":"Differential colorectal carcinogenesis: Molecular basis and clinical relevance","volume":"2","author":"A Mor\u00e1n","year":"2010","journal-title":"World J Gastrointest Oncol"},{"key":"ref137","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/1476-4598-8-90","article-title":"Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells","volume":"8","author":"H Yuzugullu","year":"2009","journal-title":"Mol Cancer"},{"key":"ref138","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.canep.2013.08.005","article-title":"Prognostic values of osteopontin-c, E-cadherin and \u03b2-catenin in breast cancer","volume":"37","author":"H Pang","year":"2013","journal-title":"Cancer Epidemiol"},{"key":"ref139","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1136\/jclinpath-2013-201467","article-title":"Clinical significance of E-cadherin, \u03b2-catenin, vimentin and S100A4 expression in completely resected squamous cell lung carcinoma","volume":"66","author":"H Zhang","year":"2013","journal-title":"J Clin Pathol"},{"key":"ref140","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.amjsurg.2012.01.002","article-title":"Beta-catenin expression is prognostic of improved non-small cell lung cancer survival","volume":"203","author":"CG Chiu","year":"2012","journal-title":"Am J Surg"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.prp.2006.03.007","article-title":"Immunohistochemical alpha- and beta-catenin and E-cadherin expression and their clinicopathological significance in human lung adenocarcinoma","volume":"202","author":"N Nozawa","year":"2006","journal-title":"Pathol Res Pract"},{"key":"ref142","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1001\/jama.2011.513","article-title":"Association of CTNNB1 (beta-catenin) alterations, body mass index, and physical activity with survival in patients with colorectal cancer","volume":"305","author":"T Morikawa","year":"2011","journal-title":"JAMA"},{"key":"ref143","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1158\/0008-5472.CAN-12-2276","article-title":"Prospective analysis of body mass index, physical activity, and colorectal cancer risk associated with \u03b2-catenin (CTNNB1) status","volume":"73","author":"T Morikawa","year":"2013","journal-title":"Cancer Res"},{"key":"ref144","doi-asserted-by":"crossref","first-page":"118","DOI":"10.3389\/fonc.2014.00118","article-title":"Prognostic Significance of \u03b2-Catenin, E-Cadherin, and SOX9 in Colorectal Cancer: Results from a Large Population-Representative Series","volume":"4","author":"J Bruun","year":"2014","journal-title":"Front Oncol"},{"key":"ref145","doi-asserted-by":"crossref","first-page":"e31827","DOI":"10.1371\/journal.pone.0031827","article-title":"Wnt5a is strongly expressed at the leading edge in non-melanoma skin cancer, forming active gradients, while canonical Wnt signalling is repressed","volume":"7","author":"C Pourreyron","year":"2012","journal-title":"PLoS One"},{"key":"ref146","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1371\/journal.pbio.0040115","article-title":"Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context","volume":"4","author":"AJ Mikels","year":"2006","journal-title":"PLoS Biol"},{"key":"ref147","first-page":"63","article-title":"The Wnt5a\/Ror2 noncanonical signaling pathway inhibits canonical Wnt signaling in K562 cells","volume":"27","author":"Y Yuan","year":"2011","journal-title":"Int J Mol Med"},{"key":"ref148","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1242\/jcs.131045","article-title":"Regulation of the phosphorylation and nuclear import and export of \u03b2-catenin by APC and its cancer-related truncated form","volume":"127","author":"L Wang","year":"2014","journal-title":"J Cell Sci"},{"key":"ref149","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1093\/carcin\/23.1.201","article-title":"AKT proto-oncogene overexpression is an early event during sporadic colon carcinogenesis","volume":"23","author":"HK Roy","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref150","doi-asserted-by":"crossref","first-page":"20315","DOI":"10.1073\/pnas.0810715105","article-title":"Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis","volume":"105","author":"PG Rychahou","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref151","article-title":"Network modeling of TGF\u03b2 signaling in hepatocellular carcinoma epithelial-to-mesenchymal transition reveals joint Sonic hedgehog and Wnt pathway activation","author":"SN Steinway","year":"2014","journal-title":"Cancer Res"},{"key":"ref152","first-page":"3858","article-title":"Growth of human hepatoma cells lines with differentiated functions in chemically defined medium","volume":"42","author":"H Nakabayashi","year":"1982","journal-title":"Cancer Res"},{"key":"ref153","first-page":"2124","article-title":"Establishment of a continuously growing cell line from primary carcinoma of the liver","volume":"50","author":"JJ Alexander","year":"1976","journal-title":"S Afr Med J"},{"key":"ref154","first-page":"22","article-title":"Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma","volume":"25","author":"Y Lin","year":"1996","journal-title":"Ann Acad Med Singapore"},{"key":"ref155","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1476-4598-7-21","article-title":"Correlation between beta-catenin mutations and expression of Wnt-signaling target genes in hepatocellular carcinoma","volume":"7","author":"M Austinat","year":"2008","journal-title":"Mol Cancer"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004571","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T08:45:45Z","timestamp":1748681145000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004571"}},"subtitle":[],"editor":[{"given":"Edwin","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,11,3]]},"references-count":155,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2015,11,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1004571","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,3]]}}}