{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:13:53Z","timestamp":1790766833993,"version":"4.1.0"},"reference-count":70,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T00:00:00Z","timestamp":1484524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T00:00:00Z","timestamp":1484524800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T00:00:00Z","timestamp":1484524800000},"content-version":"tdm","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":["NCI P01 CA129243-06"],"award-info":[{"award-number":["NCI P01 CA129243-06"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Many lines of evidence have indicated that both genetic and non-genetic determinants can contribute to intra-tumor heterogeneity and influence cancer outcomes. Among the best described sub-population of cancer cells generated by non-genetic mechanisms are cells characterized by a CD44+\/CD24\u2212 cell surface marker profile. Here, we report that human CD44+\/CD24\u2212 cancer cells are genetically highly unstable because of intrinsic defects in their DNA-repair capabilities. In fact, in CD44+\/CD24\u2212 cells, constitutive activation of the TGF-beta axis was both necessary and sufficient to reduce the expression of genes that are crucial in coordinating DNA damage repair mechanisms. Consequently, we observed that cancer cells that reside in a CD44+\/CD24\u2212 state are characterized by increased accumulation of DNA copy number alterations, greater genetic diversity and improved adaptability to drug treatment. Together, these data suggest that the transition into a CD44+\/CD24\u2212 cell state can promote intra-tumor genetic heterogeneity, spur tumor evolution and increase tumor fitness.<\/jats:p>","DOI":"10.7554\/elife.21615","type":"journal-article","created":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T08:02:33Z","timestamp":1484553753000},"source":"Crossref","is-referenced-by-count":41,"title":["TGF-\u03b2 reduces DNA ds-break repair mechanisms to heighten genetic diversity and adaptability of CD44+\/CD24\u2212 cancer cells"],"prefix":"10.7554","volume":"6","author":[{"given":"Debjani","family":"Pal","sequence":"first","affiliation":[{"name":"Cold Spring Harbor Laboratory, Cold Spring Harbor, United States"},{"name":"Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Pertot","sequence":"additional","affiliation":[{"name":"Cold Spring Harbor 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