{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:34:58Z","timestamp":1792802098764,"version":"4.5.0"},"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T00:00:00Z","timestamp":1638921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"national cancer institute","doi-asserted-by":"publisher","award":["CA231997"],"award-info":[{"award-number":["CA231997"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"national cancer institute","doi-asserted-by":"publisher","award":["CA228413"],"award-info":[{"award-number":["CA228413"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005188","name":"tobacco-related disease research program","doi-asserted-by":"publisher","award":["28IR-0046"],"award-info":[{"award-number":["28IR-0046"]}],"id":[{"id":"10.13039\/100005188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005188","name":"tobacco-related disease research program","doi-asserted-by":"publisher","award":["T30FT0824"],"award-info":[{"award-number":["T30FT0824"]}],"id":[{"id":"10.13039\/100005188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Stanford Child Health Research Institute","id":[{"id":"https:\/\/ror.org\/00we60833","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Stanford Bio-X Undergraduate Summer Research"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    The retinoblastoma (RB) tumor suppressor is functionally inactivated in a wide range of human tumors where this inactivation promotes tumorigenesis in part by allowing uncontrolled proliferation. RB has been extensively studied, but its mechanisms of action in normal and cancer cells remain only partly understood. Here, we describe a new mouse model to investigate the consequences of RB depletion and its re-activation\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In these mice, induction of shRNA molecules targeting RB for knock-down results in the development of phenotypes similar to\n                    <jats:italic>Rb<\/jats:italic>\n                    knock-out mice, including the development of pituitary and thyroid tumors. Re-expression of RB leads to cell cycle arrest in cancer cells and repression of transcriptional programs driven by E2F activity. Thus, continuous RB loss is required for the maintenance of tumor phenotypes initiated by loss of RB, and this new mouse model will provide a new platform to investigate RB function\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1009941","type":"journal-article","created":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T13:41:54Z","timestamp":1638970914000},"page":"e1009941","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["RB depletion is required for the continuous growth of tumors initiated by loss of RB"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7247-2256","authenticated-orcid":true,"given":"Alex","family":"Doan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2357-1119","authenticated-orcid":true,"given":"Julia","family":"Arand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0664-7967","authenticated-orcid":true,"given":"Diana","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9081-9850","authenticated-orcid":true,"given":"Alexandros P.","family":"Drainas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan Ting","family":"Shue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7051-5822","authenticated-orcid":true,"given":"Myung Chang","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6220-5998","authenticated-orcid":true,"given":"Shuyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4632-5113","authenticated-orcid":true,"given":"David M.","family":"Walter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea C.","family":"Chaikovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5975-864X","authenticated-orcid":true,"given":"David M.","family":"Feldser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7048-1418","authenticated-orcid":true,"given":"Lukas E.","family":"Dow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Skotheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8928-9968","authenticated-orcid":true,"given":"Julien","family":"Sage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,12,8]]},"reference":[{"issue":"2","key":"pgen.1009941.ref001","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0092-8674(03)01075-4","article-title":"Principles of tumor suppression","volume":"116","author":"CJ Sherr","year":"2004","journal-title":"Cell"},{"issue":"5","key":"pgen.1009941.ref002","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"D Hanahan","year":"2011","journal-title":"Cell"},{"key":"pgen.1009941.ref003","first-page":"1","volume-title":"D-type Cyclins and Cancer","author":"CJ Sherr","year":"2018"},{"issue":"5293","key":"pgen.1009941.ref004","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1126\/science.274.5293.1672","article-title":"Cancer cell cycles","volume":"274","author":"CJ Sherr","year":"1996","journal-title":"Science"},{"issue":"13","key":"pgen.1009941.ref005","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1101\/gad.282145.116","article-title":"RB1: a prototype tumor suppressor and an enigma","volume":"30","author":"NJ Dyson","year":"2016","journal-title":"Genes Dev"},{"issue":"6","key":"pgen.1009941.ref006","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/s41568-019-0143-7","article-title":"The broken cycle: E2F dysfunction in cancer","volume":"19","author":"LN Kent","year":"2019","journal-title":"Nat Rev Cancer"},{"issue":"2","key":"pgen.1009941.ref007","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.molcel.2020.08.020","article-title":"Integrating Old and New Paradigms of G1\/S Control","volume":"80","author":"SM Rubin","year":"2020","journal-title":"Mol Cell"},{"issue":"1","key":"pgen.1009941.ref008","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.tibs.2012.10.007","article-title":"Deciphering the retinoblastoma protein phosphorylation code","volume":"38","author":"SM Rubin","year":"2013","journal-title":"Trends in biochemical sciences"},{"issue":"4","key":"pgen.1009941.ref009","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1158\/2159-8290.CD-15-0894","article-title":"Targeting CDK4 and CDK6: From Discovery to Therapy","volume":"6","author":"CJ Sherr","year":"2016","journal-title":"Cancer Discov"},{"issue":"2","key":"pgen.1009941.ref010","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nrc.2016.138","article-title":"Cell cycle proteins as promising targets in cancer therapy","volume":"17","author":"T Otto","year":"2017","journal-title":"Nat Rev Cancer"},{"issue":"20","key":"pgen.1009941.ref011","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1056\/NEJMoa1607303","article-title":"Palbociclib and Letrozole in Advanced Breast Cancer","volume":"375","author":"RS Finn","year":"2016","journal-title":"N Engl J Med"},{"issue":"20","key":"pgen.1009941.ref012","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1056\/NEJMoa1810527","article-title":"Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer","volume":"379","author":"NC Turner","year":"2018","journal-title":"N Engl J Med"},{"key":"pgen.1009941.ref013","article-title":"Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer","author":"DJ Slamon","year":"2019","journal-title":"N Engl J Med"},{"key":"pgen.1009941.ref014","article-title":"The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial","author":"GW Sledge","year":"2019","journal-title":"JAMA Oncol"},{"issue":"7","key":"pgen.1009941.ref015","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1158\/2159-8290.CD-16-0095","article-title":"Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors","volume":"6","author":"A Patnaik","year":"2016","journal-title":"Cancer Discov."},{"issue":"1","key":"pgen.1009941.ref016","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.cllc.2015.08.003","article-title":"Treatment Rationale and Study Design for the JUNIPER Study: A Randomized Phase III Study of Abemaciclib With Best Supportive Care Versus Erlotinib With Best Supportive Care in Patients With Stage IV Non-Small-Cell Lung Cancer With a Detectable KRAS Mutation Whose Disease Has Progressed After Platinum-Based Chemotherapy","volume":"17","author":"JW Goldman","year":"2016","journal-title":"Clin Lung Cancer"},{"issue":"1","key":"pgen.1009941.ref017","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1158\/2159-8290.CD-18-0830","article-title":"PTEN Loss Mediates Clinical Cross-Resistance to CDK4\/6 and PI3Kalpha Inhibitors in Breast Cancer","volume":"10","author":"C Costa","year":"2020","journal-title":"Cancer Discov"},{"issue":"7756","key":"pgen.1009941.ref018","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/s41586-019-1172-9","article-title":"RB constrains lineage fidelity and multiple stages of tumour progression and metastasis","volume":"569","author":"DM Walter","year":"2019","journal-title":"Nature"},{"issue":"8","key":"pgen.1009941.ref019","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1158\/2159-8290.CD-19-1390","article-title":"The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4\/6 Inhibitors in Patients with Hormone Receptor-Positive Metastatic Breast Cancer","volume":"10","author":"SA Wander","year":"2020","journal-title":"Cancer Discov"},{"key":"pgen.1009941.ref020","first-page":"1","article-title":"Distinct CDK6 complexes determine tumor cell response to CDK4\/6 inhibitors and degraders","author":"X Wu","year":"2021","journal-title":"Nature Cancer"},{"issue":"1","key":"pgen.1009941.ref021","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/1535-7163.MCT-19-0253","article-title":"The Ongoing Search for Biomarkers of CDK4\/6 Inhibitor Responsiveness in Breast Cancer","volume":"19","author":"SF Schoninger","year":"2020","journal-title":"Mol Cancer Ther"},{"issue":"9","key":"pgen.1009941.ref022","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1101\/gad.7.9.1654","article-title":"Expression of a retinoblastoma transgene results in dwarf mice","volume":"7","author":"YJ Bignon","year":"1993","journal-title":"Genes Dev"},{"issue":"12","key":"pgen.1009941.ref023","first-page":"1057","article-title":"Quantitative effects of the retinoblastoma gene on mouse development and tissue-specific tumorigenesis","volume":"4","author":"C-Y Chang","year":"1993","journal-title":"Cell growth & differentiation: the molecular biology journal of the American Association for Cancer Research"},{"issue":"7","key":"pgen.1009941.ref024","doi-asserted-by":"crossref","first-page":"3916","DOI":"10.1073\/pnas.96.7.3916","article-title":"RB-mediated suppression of spontaneous multiple neuroendocrine neoplasia and lung metastases in Rb+\/- mice","volume":"96","author":"AY Nikitin","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pgen.1009941.ref025","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1128\/MCB.22.9.3103-3110.2002","article-title":"Tumor suppression by a severely truncated species of retinoblastoma protein","volume":"22","author":"H Yang","year":"2002","journal-title":"Mol Cell Biol"},{"key":"pgen.1009941.ref026","doi-asserted-by":"crossref","first-page":"8783","DOI":"10.1038\/ncomms9783","article-title":"Recombinase-based conditional and reversible gene regulation via XTR alleles","volume":"6","author":"C Robles-Oteiza","year":"2015","journal-title":"Nature communications"},{"issue":"2","key":"pgen.1009941.ref027","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nprot.2011.446","article-title":"A pipeline for the generation of shRNA transgenic mice","volume":"7","author":"LE Dow","year":"2012","journal-title":"Nat Protoc"},{"issue":"6","key":"pgen.1009941.ref028","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1016\/j.celrep.2013.11.020","article-title":"An optimized microRNA backbone for effective single-copy RNAi","volume":"5","author":"C Fellmann","year":"2013","journal-title":"Cell Rep"},{"issue":"1","key":"pgen.1009941.ref029","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cell.2011.03.012","article-title":"A rapid and scalable system for studying gene function in mice using conditional RNA interference","volume":"145","author":"PK Premsrirut","year":"2011","journal-title":"Cell"},{"issue":"1","key":"pgen.1009941.ref030","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/gene.20180","article-title":"Efficient method to generate single-copy transgenic mice by site-specific integration in embryonic stem cells","volume":"44","author":"C Beard","year":"2006","journal-title":"Genesis"},{"issue":"1","key":"pgen.1009941.ref031","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1074\/jbc.M509053200","article-title":"The related retinoblastoma (pRb) and p130 proteins cooperate to regulate homeostasis in the intestinal epithelium","volume":"281","author":"K Haigis","year":"2006","journal-title":"J Biol Chem"},{"issue":"6393","key":"pgen.1009941.ref032","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/359328a0","article-title":"Requirement for a functional Rb-1 gene in murine development","volume":"359","author":"AR Clarke","year":"1992","journal-title":"Nature"},{"issue":"6393","key":"pgen.1009941.ref033","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/359295a0","article-title":"Effects of an Rb mutation in the mouse","volume":"359","author":"T Jacks","year":"1992","journal-title":"Nature"},{"issue":"10","key":"pgen.1009941.ref034","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1158\/1541-7786.MCR-18-0201","article-title":"Beyond the Cell Cycle: Enhancing the Immune Surveillance of Tumors Via CDK4\/6 Inhibition","volume":"16","author":"AC Chaikovsky","year":"2018","journal-title":"Mol Cancer Res"},{"issue":"1","key":"pgen.1009941.ref035","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1136\/gutjnl-2020-321000","article-title":"Targeting dual signalling pathways in concert with immune checkpoints for the treatment of pancreatic cancer","volume":"70","author":"ES Knudsen","year":"2021","journal-title":"Gut"},{"issue":"18","key":"pgen.1009941.ref036","doi-asserted-by":"crossref","first-page":"6542","DOI":"10.1128\/MCB.23.18.6542-6552.2003","article-title":"E2F3 loss has opposing effects on different pRB-deficient tumors, resulting in suppression of pituitary tumors but metastasis of medullary thyroid carcinomas","volume":"23","author":"U Ziebold","year":"2003","journal-title":"Mol Cell Biol"},{"issue":"8","key":"pgen.1009941.ref037","first-page":"1615","article-title":"Effects of heterozygosity for the Rb-1t19neo allele in the mouse","volume":"10","author":"DJ Harrison","year":"1995","journal-title":"Oncogene"},{"issue":"6","key":"pgen.1009941.ref038","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S1535-6108(02)00207-6","article-title":"E2F4 loss suppresses tumorigenesis in Rb mutant mice","volume":"2","author":"EY Lee","year":"2002","journal-title":"Cancer Cell"},{"issue":"6","key":"pgen.1009941.ref039","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1128\/MCB.01854-06","article-title":"Selective requirements for E2f3 in the development and tumorigenicity of Rb-deficient chimeric tissues","volume":"27","author":"T Parisi","year":"2007","journal-title":"Mol Cell Biol"},{"issue":"11","key":"pgen.1009941.ref040","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1073\/pnas.1523693113","article-title":"Pten loss promotes MAPK pathway dependency in HER2\/neu breast carcinomas","volume":"113","author":"SH Ebbesen","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"11","key":"pgen.1009941.ref041","doi-asserted-by":"crossref","first-page":"6546","DOI":"10.1073\/pnas.1031853100","article-title":"Rb function in extraembryonic lineages suppresses apoptosis in the CNS of Rb-deficient mice","volume":"100","author":"A de Bruin","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6926","key":"pgen.1009941.ref042","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/nature01417","article-title":"Extra-embryonic function of Rb is essential for embryonic development and viability","volume":"421","author":"L Wu","year":"2003","journal-title":"Nature"},{"issue":"1","key":"pgen.1009941.ref043","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sj.onc.1202169","article-title":"Flp-mediated tissue-specific inactivation of the retinoblastoma tumor suppressor gene in the mouse","volume":"17","author":"M Vooijs","year":"1998","journal-title":"Oncogene"},{"issue":"1","key":"pgen.1009941.ref044","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.stem.2014.10.019","article-title":"Inhibition of pluripotency networks by the Rb tumor suppressor restricts reprogramming and tumorigenesis","volume":"16","author":"MS Kareta","year":"2015","journal-title":"Cell Stem Cell"},{"issue":"6320","key":"pgen.1009941.ref045","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1126\/science.aah4199","article-title":"Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance","volume":"355","author":"SY Ku","year":"2017","journal-title":"Science"},{"issue":"6320","key":"pgen.1009941.ref046","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1126\/science.aah4307","article-title":"SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer","volume":"355","author":"P Mu","year":"2017","journal-title":"Science"},{"issue":"1","key":"pgen.1009941.ref047","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1124\/jpet.118.252064","article-title":"Plasma and Brain Concentrations of Doxycycline after Single and Repeated Doses in Wild-Type and APP23 Mice","volume":"368","author":"J Lucchetti","year":"2019","journal-title":"J Pharmacol Exp Ther"},{"issue":"7","key":"pgen.1009941.ref048","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.cell.2015.05.033","article-title":"Apc Restoration Promotes Cellular Differentiation and Reestablishes Crypt Homeostasis in Colorectal Cancer","volume":"161","author":"LE Dow","year":"2015","journal-title":"Cell"},{"issue":"11","key":"pgen.1009941.ref049","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1038\/nmeth.2640","article-title":"Inducible control of gene expression with destabilized Cre","volume":"10","author":"R Sando","year":"2013","journal-title":"Nat Methods"},{"issue":"1","key":"pgen.1009941.ref050","doi-asserted-by":"crossref","first-page":"5701","DOI":"10.1038\/s41467-020-19532-z","article-title":"The auxin-inducible degron 2 technology provides sharp degradation control in yeast, mammalian cells, and mice","volume":"11","author":"A Yesbolatova","year":"2020","journal-title":"Nat Commun."},{"issue":"2","key":"pgen.1009941.ref051","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s11060-006-9316-9","article-title":"Promoter hypermethylation profile of cell cycle regulator genes in pituitary adenomas","volume":"83","author":"A Yoshino","year":"2007","journal-title":"J Neurooncol"},{"issue":"5","key":"pgen.1009941.ref052","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1093\/jnen\/64.5.398","article-title":"The p15(INK4b)\/p16(INK4a)\/RB1 pathway is frequently deregulated in human pituitary adenomas","volume":"64","author":"A Ogino","year":"2005","journal-title":"J Neuropathol Exp Neurol"},{"issue":"5","key":"pgen.1009941.ref053","first-page":"1211","article-title":"Loss of pRb expression in pituitary adenomas is associated with methylation of the RB1 CpG island","volume":"60","author":"DJ Simpson","year":"2000","journal-title":"Cancer Res"},{"issue":"12","key":"pgen.1009941.ref054","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12123566","article-title":"Combined CDK2 and CDK4\/6 Inhibition Overcomes Palbociclib Resistance in Breast Cancer by Enhancing Senescence","volume":"12","author":"K Pandey","year":"2020","journal-title":"Cancers (Basel)."},{"key":"pgen.1009941.ref055","article-title":"Functional determinants of cell-cycle plasticity and sensitivity to CDK4\/6 inhibition","author":"V Kumarasamy","year":"2020","journal-title":"Cancer Res"},{"issue":"2","key":"pgen.1009941.ref056","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/his.13516","article-title":"Validation of the systematic scoring of immunohistochemically stained tumour tissue microarrays using QuPath digital image analysis","volume":"73","author":"MB Loughrey","year":"2018","journal-title":"Histopathology"},{"issue":"12","key":"pgen.1009941.ref057","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"issue":"W1","key":"pgen.1009941.ref058","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"MV Kuleshov","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"pgen.1009941.ref059","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1471-2105-10-48","article-title":"GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists","volume":"10","author":"E Eden","year":"2009","journal-title":"BMC Bioinformatics"},{"issue":"7","key":"pgen.1009941.ref060","doi-asserted-by":"crossref","first-page":"e21800","DOI":"10.1371\/journal.pone.0021800","article-title":"REVIGO summarizes and visualizes long lists of gene ontology terms","volume":"6","author":"F Supek","year":"2011","journal-title":"PLoS One"},{"issue":"28","key":"pgen.1009941.ref061","doi-asserted-by":"crossref","first-page":"3943","DOI":"10.1038\/onc.2016.502","article-title":"evaluation of p53 target genes","volume":"36","author":"Fischer M. Census","year":"2017","journal-title":"Oncogene"}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009941","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T13:43:03Z","timestamp":1638970983000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009941"}},"subtitle":[],"editor":[{"given":"Bruce E.","family":"Clurman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,8]]},"references-count":61,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1009941","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,8]]}}}