{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:29:39Z","timestamp":1778819379961,"version":"3.51.4"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2015,3,5]],"date-time":"2015-03-05T00:00:00Z","timestamp":1425513600000},"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.1004025","type":"journal-article","created":{"date-parts":[[2015,3,5]],"date-time":"2015-03-05T19:03:27Z","timestamp":1425582207000},"page":"e1004025","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":66,"title":["Evolution and Phenotypic Selection of Cancer Stem Cells"],"prefix":"10.1371","volume":"11","author":[{"given":"Jan","family":"Poleszczuk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Hahnfeldt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heiko","family":"Enderling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,3,5]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0014-4827(61)90192-6","article-title":"The serial cultivation of human diploid cell strains","volume":"25","author":"L Hayflick","year":"1961","journal-title":"Experimental Cell Research"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/0014-4827(65)90211-9","article-title":"The limited in vitro lifetime of human diploid cell strains","volume":"37","author":"L Hayflick","year":"1965","journal-title":"Experimental Cell Research"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1046\/j.1365-2184.2003.00264.x","article-title":"The small intestine as a model for evaluating adult tissue stem cell drug targets","volume":"36","author":"CS Potten","year":"2003","journal-title":"Cell Proliferation"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0022-5193(03)00090-0","article-title":"Oscillations in cyclical neutropenia: new evidence based on mathematical modeling","volume":"223","author":"S Bernard","year":"2003","journal-title":"Journal of Theoretical Biology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/35102167","article-title":"Stem cells, cancer, and cancer stem cells","volume":"414","author":"T Reya","year":"2001","journal-title":"Nature"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nrc3597","article-title":"Unravelling cancer stem cell potential","volume":"13","author":"B Beck","year":"2013","journal-title":"Nature Reviews Cancer"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/ncb2889","article-title":"Stem cell quiescence acts as a tumour suppressor in squamous tumours","volume":"16","author":"AC White","year":"2014","journal-title":"Nature Cell Biology"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.4161\/cc.9.13.12149","article-title":"Muscle stem cells and reversible quiescence: the role of sprouty","volume":"9","author":"R Abou-Khalil","year":"2010","journal-title":"Cell Cycle"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"e1000447","DOI":"10.1371\/journal.pcbi.1000447","article-title":"Stem Cell Proliferation and Quiescence\u2014Two Sides of the Same Coin","volume":"5","author":"I Glauche","year":"2009","journal-title":"PLoS Comput Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nrm3591","article-title":"Molecular regulation of stem cell quiescence","volume":"14","author":"TH Cheung","year":"2013","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nrc1740","article-title":"Opinion: The origin of the cancer stem cell: current controversies and new insights","volume":"5","author":"R Bjerkvig","year":"2005","journal-title":"Nature Reviews Cancer"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/nature09781","article-title":"Cells of origin in cancer","volume":"469","author":"JE Visvader","year":"2011","journal-title":"Nature"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/nature07602","article-title":"Crypt stem cells as the cells-of-origin of intestinal cancer","volume":"457","author":"N Barker","year":"2008","journal-title":"Nature"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"16616","DOI":"10.1073\/pnas.0908107106","article-title":"A progenitor cell origin of myeloid malignancies","volume":"106","author":"H Haeno","year":"2009","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e24454","DOI":"10.1371\/journal.pone.0024454","article-title":"The probable cell of origin of NF1- and PDGF-driven glioblastomas","volume":"6","author":"D Hambardzumyan","year":"2011","journal-title":"PLoS ONE"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"8814","DOI":"10.1158\/0008-5472.CAN-09-2115","article-title":"Paradoxical Dependencies of Tumor Dormancy and Progression on Basic Cell Kinetics","volume":"69","author":"H Enderling","year":"2009","journal-title":"Cancer Research"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/978-1-4614-1445-2_4","article-title":"Cancer stem cells and tumor dormancy","volume":"734","author":"H Enderling","year":"2013","journal-title":"Adv Exp Med Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1056\/NEJM199304293281706","article-title":"Advances in diagnostic imaging and overestimations of disease prevalence and the benefits of therapy","volume":"328","author":"WC Black","year":"1993","journal-title":"New England Journal of Medicine"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1093\/jnci\/djq099","article-title":"Overdiagnosis in Cancer","volume":"102","author":"HG Welch","year":"2010","journal-title":"JNCI Journal of the National Cancer Institute"},{"key":"ref20","doi-asserted-by":"crossref","DOI":"10.1515\/9780691186863","article-title":"Dynamics of Cancer","author":"SA Frank","year":"2007"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0022-2836(78)90294-2","article-title":"A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena","volume":"120","author":"EH Blackburn","year":"1978","journal-title":"J Mol Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0022-5193(73)90198-7","article-title":"A theory of marginotomy: the incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon","volume":"41","author":"AM Olovnikov","year":"1973","journal-title":"Journal of Theoretical Biology"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/345458a0","article-title":"Telomeres shorten during ageing of human fibroblasts","volume":"345","author":"CB Harley","year":"1990","journal-title":"Nature"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/0092-8674(85)90170-9","article-title":"Identification of a specific telomere terminal transferase activity in Tetrahymena extracts","volume":"43","author":"CW Greider","year":"1985","journal-title":"Cell"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1182\/blood-2002-07-2334","article-title":"Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation","volume":"102","author":"RC Allsopp","year":"2003","journal-title":"Blood"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"3819","DOI":"10.1016\/j.febslet.2010.05.026","article-title":"Telomeres and telomerase in normal and cancer stem cells","volume":"584","author":"JW Shay","year":"2010","journal-title":"FEBS Letters"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1038\/sj.bjc.6605071","article-title":"Migration rules: tumours are conglomerates of self-metastases","volume":"100","author":"H Enderling","year":"2009","journal-title":"Br J Cancer"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1745-6150-5-23","article-title":"Tumor morphological evolution: directed migration and gain and loss of the self-metastatic phenotype","volume":"5","author":"H Enderling","year":"2010","journal-title":"Biol Direct"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1634\/theoncologist.10-6-370","article-title":"Conceptual and Practical Implications of Breast Tissue Geometry: Toward a More Effective, Less Toxic Therapy","volume":"10","author":"L Norton","year":"2005","journal-title":"The Oncologist"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1742-4682-8-48","article-title":"Non-stem cancer cell kinetics modulate solid tumor progression","volume":"8","author":"CI Morton","year":"2011","journal-title":"Theoretical Biology and Medical Modelling"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11538-012-9798-x","article-title":"The tumor growth paradox and immune system-mediated selection for cancer stem cells","volume":"75","author":"T Hillen","year":"2013","journal-title":"Bull Math Biol"},{"key":"ref32","first-page":"276","article-title":"The Transmission of Leukemia of Mice with a Single Cell","volume":"31","author":"J Furth","year":"1937","journal-title":"The American Journal of Cancer"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.1073\/pnas.0530291100","article-title":"Prospective identification of tumorigenic breast cancer cells","volume":"100","author":"M Al-Hajj","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref34","first-page":"5821","article-title":"Identification of a cancer stem cell in human brain tumors","volume":"63","author":"SK Singh","year":"2003","journal-title":"Cancer Research"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1158\/0008-5472.CAN-09-3663","article-title":"Cancer Stem Cell Tumor Model Reveals Invasive Morphology and Increased Phenotypical Heterogeneity","volume":"70","author":"A Sottoriva","year":"2010","journal-title":"Cancer Research"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.semcancer.2011.10.001","article-title":"Role of telomeres and telomerase in cancer","volume":"21","author":"JW Shay","year":"2011","journal-title":"Seminars in Cancer Biology"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1113205","article-title":"Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing","volume":"366","author":"M Gerlinger","year":"2012","journal-title":"N Engl J Med"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nature07567","article-title":"Efficient tumour formation by single human melanoma cells","volume":"456","author":"E Quintana","year":"2008","journal-title":"Nature"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1126\/science.1142596","article-title":"Tumor Growth Need Not Be Driven by Rare Cancer Stem Cells","volume":"317","author":"PN Kelly","year":"2007","journal-title":"Science"},{"key":"ref40","first-page":"193","article-title":"Cancer Stem Cell Kinetics","author":"H Enderling","year":"2013"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3389\/fonc.2013.00076","article-title":"Cancer stem cells: a minor cancer subpopulation that redefines global cancer features","volume":"3","author":"H Enderling","year":"2013","journal-title":"Front Oncol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1096\/fj.05-3946fje","article-title":"Prolonged dormancy of human liposarcoma is associated with impaired tumor angiogenesis","volume":"20","author":"N Almog","year":"2006","journal-title":"The FASEB Journal"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1093\/jnci\/djj068","article-title":"A Model of Human Tumor Dormancy: An Angiogenic Switch From the Nonangiogenic Phenotype","volume":"98","author":"MJ Folkman","year":"2006","journal-title":"JNCI Journal of the National Cancer Institute"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1158\/0008-5472.CAN-08-2590","article-title":"Transcriptional Switch of Dormant Tumors to Fast-Growing Angiogenic Phenotype","volume":"69","author":"A Abdollahi","year":"2009","journal-title":"Cancer Research"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/cpr.12101","article-title":"Biphasic modulation of cancer stem cell-driven solid tumour dynamics in response to reactivated replicative senescence","volume":"47","author":"J Poleszczuk","year":"2014","journal-title":"Cell Prolif"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"e1003433","DOI":"10.1371\/journal.pcbi.1003433","article-title":"Microenvironmental variables must influence intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity","volume":"10","author":"JG Scott","year":"2014","journal-title":"PLoS Comput Biol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/1742-4682-9-36","article-title":"Spatiotemporal dynamics of the biological interface between cancer and the microenvironment: a fractal anomalous diffusion model with microenvironment plasticity","volume":"9","author":"F-C Tsai","year":"2012","journal-title":"Theoretical Biology and Medical Modelling"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/cr.2012.13","article-title":"Understanding cancer stem cell heterogeneity and plasticity","volume":"22","author":"DG Tang","year":"2012","journal-title":"Cell Res"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1373\/clinchem.2012.184655","article-title":"Cell Plasticity and Heterogeneity in Cancer","volume":"59","author":"ND Marjanovic","year":"2013","journal-title":"Clinical Chemistry"},{"key":"ref50","doi-asserted-by":"crossref","unstructured":"Prokharau PA, Vermolen FJ, Garc\u00eda-Aznar JM (2012) A mathematical model for cell differentiation, as an evolutionary and regulated process. Comput Methods Biomech Biomed Engin.","DOI":"10.1080\/10255842.2012.736503"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"e14366","DOI":"10.1371\/journal.pone.0014366","article-title":"The therapeutic implications of plasticity of the cancer stem cell phenotype","volume":"5","author":"K Leder","year":"2010","journal-title":"PLoS ONE"},{"key":"ref52","doi-asserted-by":"crossref","unstructured":"Yamaguchi H, Wyckoff J, Condeelis J (2005) Cell migration in tumors. Current Opinion in Cell Biology.","DOI":"10.1016\/j.ceb.2005.08.002"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1086\/280418","article-title":"Some genetic aspects of sex","volume":"66","author":"HJ Muller","year":"1932","journal-title":"Am Nat"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.tpb.2007.10.004","article-title":"The traveling-wave approach to asexual evolution: Muller&apos;s ratchet and speed of adaptation","volume":"73","author":"IM Rouzine","year":"2008","journal-title":"Theoretical Population Biology"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/sj.clpt.6100202","article-title":"Symmetric Division of Cancer Stem Cells\u2014a Key Mechanism in Tumor Growth that should be Targeted in Future Therapeutic Approaches","volume":"81","author":"BM Boman","year":"2007","journal-title":"Clin Pharmacol Ther"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1593\/neo.08572","article-title":"Pathways to tumorigenesis\u2014modeling mutation acquisition in stem cells and their progeny","volume":"10","author":"R Ashkenazi","year":"2008","journal-title":"Neoplasia"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0921-8734(91)90018-7","article-title":"Telomere loss: mitotic clock or genetic time bomb?","volume":"256","author":"CB Harley","year":"1991","journal-title":"Mutation Research\/DNAging"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"144","DOI":"10.4236\/am.2014.51017","article-title":"A High-Performance Cellular Automaton Model of Tumor Growth with Dynamically Growing Domains","volume":"05","author":"H Enderling","year":"2014","journal-title":"Applied Mathematics"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/255197a0","article-title":"Mutation selection and the natural history of cancer","volume":"255","author":"J Cairns","year":"1975","journal-title":"Nature"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"041914","DOI":"10.1103\/PhysRevE.71.041914","article-title":"Evolutionary dynamics of adult stem cells: comparison of random and immortal-strand segregation mechanisms","volume":"71","author":"E Tannenbaum","year":"2005","journal-title":"Phys Rev E"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/eva.12030","article-title":"An evolutionary explanation for the presence of cancer nonstem cells in neoplasms","volume":"6","author":"K Sprouffske","year":"2012","journal-title":"Evol Appl"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/imammb\/dqi005","article-title":"A hybrid mathematical model of solid tumour invasion: the importance of cell adhesion","volume":"22","author":"ARA Anderson","year":"2005","journal-title":"Mathematical Medicine and Biology"},{"key":"ref63","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"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T16:14:13Z","timestamp":1589040853000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004025"}},"subtitle":[],"editor":[{"given":"Andrey","family":"Rzhetsky","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,3,5]]},"references-count":63,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2015,3,5]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1004025","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,5]]}}}