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The prevailing explanation is that each proliferating cancer cell has acquired unlimited replicative capacity, yet this does not explain why the overwhelming majority of cancer cells fail to initiate tumors on transplantation, why the cancer stem cell fraction of serially passaged cultures remains nearly constant, or why the measured cell loss factor of human tumors is so high. This review proposes an alternative reading of these observations. Non\u2010stem cancer cells may possess a replicative lifespan that is set not by telomere attrition but by the progressive accumulation of damaged proteins, protein aggregates and dysfunctional mitochondria, so that each lineage eventually terminates in growth arrest or death. Persistent expansion would then depend on th e rate at which non\u2010stem cancer cells are converted back into stem cells. Work on transforming growth factor\u2010\u03b2 associated molecules, including TMEPAI\/PMEPA1, MAFK\u2013GPNMB and THG\u20101, is reviewed in this light, together with evidence from budding yeast and mammalian stem cells that damage is partitioned asymmetrically at division. Established observations, reasonable inferences and untested assumptions are distinguished explicitly, and experimental tests are proposed.<\/jats:p>","DOI":"10.1111\/pin.70188","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:04:15Z","timestamp":1791439455000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Why Most Cancer Cells Cannot Form Tumors: Replicative Lifespan, Damage Partitioning and Stem Cell Induction"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9905-2473","authenticated-orcid":false,"given":"Mitsuyasu","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Experimental Pathology, Institute of Medicine University of Tsukuba Tsukuba Japan"},{"name":"Faculty of Pharmacy Universitas Indonesia, Kampus UI Depok Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan D.","year":"2022","journal-title":"Cancer Discovery"},{"key":"e_1_2_16_3_1","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":"Hanahan D.","year":"2011","journal-title":"Cell"},{"issue":"7","key":"e_1_2_16_4_1","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nm0797-730","article-title":"Human Acute Myeloid Leukemia Is Organized as a Hierarchy That Originates From a Primitive Hematopoietic Cell","volume":"3","author":"Bonnet D.","year":"1997","journal-title":"Nature Medicine"},{"key":"e_1_2_16_5_1","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.1073\/pnas.0530291100","article-title":"Prospective Identification of Tumorigenic Breast Cancer Cells","volume":"100","author":"Al\u2010Hajj M.","year":"2003","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"e_1_2_16_6_1","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nature07567","article-title":"Efficient Tumour Formation by Single Human Melanoma Cells","volume":"456","author":"Quintana E.","year":"2008","journal-title":"Nature"},{"key":"e_1_2_16_7_1","doi-asserted-by":"crossref","first-page":"7950","DOI":"10.1073\/pnas.1102454108","article-title":"Normal and Neoplastic Nonstem Cells can Spontaneously Convert to a Stem\u2010Like State","volume":"108","author":"Chaffer C. 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E.","year":"1978","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"e_1_2_16_36_1","doi-asserted-by":"crossref","first-page":"5339","DOI":"10.1073\/pnas.78.9.5339","article-title":"New Class of Transforming Growth Factors Potentiated by Epidermal Growth Factor: Isolation From Non\u2010Neoplastic Tissues","volume":"78","author":"Roberts A. B.","year":"1981","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"e_1_2_16_37_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1073\/pnas.82.1.119","article-title":"Type Beta Transforming Growth Factor: A Bifunctional Regulator of Cellular Growth","volume":"82","author":"Roberts A. B.","year":"1985","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"e_1_2_16_38_1","doi-asserted-by":"crossref","first-page":"6264","DOI":"10.1073\/pnas.80.20.6264","article-title":"Sarcoma Growth Factor From Conditioned Medium of Virally Transformed Cells Is Composed of Both Type Alpha and Type Beta Transforming Growth Factors","volume":"80","author":"Anzano M. A.","year":"1983","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"e_1_2_16_39_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.virol.2011.02.002","article-title":"Activation of the TGF\u2010\u03b2\/Smad Signaling Pathway in Oncogenic Transformation by v\u2010Rel","volume":"413","author":"Tiwari R.","year":"2011","journal-title":"Virology"},{"key":"e_1_2_16_40_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.cell.2008.07.001","article-title":"TGF\u03b2 in Cancer","volume":"134","author":"Massagu\u00e9 J.","year":"2008","journal-title":"Cell"},{"key":"e_1_2_16_41_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/ng1001-117","article-title":"TGF\u2010\u03b2 Signaling in Tumor Suppression and Cancer Progression","volume":"29","author":"Derynck R.","year":"2001","journal-title":"Nature Genetics"},{"key":"e_1_2_16_42_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.molcel.2009.10.028","article-title":"Tmepai, a Transmembrane TGF\u2010\u03b2\u2010inducible Protein, Sequesters Smad Proteins From Active Participation in TGF\u2010\u03b2 Signaling","volume":"37","author":"Watanabe Y.","year":"2010","journal-title":"Molecular Cell"},{"key":"e_1_2_16_43_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/cas.12355","article-title":"TMEPAI\/PMEPA1 Enhances Tumorigenic Activities in Lung Cancer Cells","volume":"105","author":"Vo Nguyen T. 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P.","year":"2019","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"e_1_2_16_52_1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1158\/1541-7786.MCR-24-0120","article-title":"THG\u20101\/TSC22D4 Promotes IL\u20101 Signaling Through Stabilization of TRAF6 in Squamous Cell Carcinoma","volume":"23","author":"Okano Y.","year":"2025","journal-title":"Molecular Cancer Research"},{"key":"e_1_2_16_53_1","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":"Hayflick L.","year":"1961","journal-title":"Experimental Cell Research"},{"key":"e_1_2_16_54_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1126\/science.279.5349.349","article-title":"Extension of Life\u2010Span by Introduction of Telomerase Into Normal Human Cells","volume":"279","author":"Bodnar A. G.","year":"1998","journal-title":"Science"},{"key":"e_1_2_16_55_1","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/S0531-5565(00)00180-7","article-title":"Cellular and Molecular Mechanisms of Stress\u2010Induced Premature Senescence (SIPS) of Human Diploid Fibroblasts and Melanocytes","volume":"35","author":"Toussaint O.","year":"2000","journal-title":"Experimental Gerontology"},{"key":"e_1_2_16_56_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev.cellbio.23.090506.123509","article-title":"Replicative Aging in Yeast: The Means to the End","volume":"24","author":"Steinkraus K. 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