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Plasticity in Colorectal Cancer: Why Cancer Cells Differentiate

Walter, Romina Judith; Sonnentag, Steffen Joachim; Orian-Rousseau, Véronique; Munoz-Sagredo, Leonel

Abstract:
The cancer stem cell hypothesis poses that the bulk of differentiated cells are non-tumorigenic and only a subset of cells with self-renewal capabilities drive tumor initiation and progression. This means that differentiation could have a tumor-suppressive effect. Accumulating evidence shows, however, that in some solid tumors, like colorectal cancer, such a hierarchical organization is necessary. The identification of Lgr5 as a reliable marker of normal intestinal epithelial stem cells, together with strategies to trace cell lineages within tumors and the possibility to selectively ablate these cells, have proven the relevance of Lgr5+ cells for cancer progression. On the contrary, the role of Lgr5− cells during this process remains largely unknown. In this review, we explore available evidence pointing towards possible selective advantages of cancer cells organized hierarchically and its resulting cell heterogeneity. Clear evidence of plasticity between cell states, in which loss of Lgr5+ cells can be replenished by dedifferentiation of Lgr5− cells, shows that cell hierarchies could grant adaptive traits to tumors upon changing selective pressures, including those derived from anticancer therapy, as well as during tumor progression to metastasis.

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Verlagsausgabe §
DOI: 10.5445/IR/1000129955
Veröffentlicht am 23.02.2021
Originalveröffentlichung
DOI: 10.3390/cancers13040918
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2021
Sprache Englisch
Identifikator ISSN: 2072-6694
KITopen-ID: 1000129955
Erschienen in Cancers
Verlag MDPI
Band 13
Heft 4
Seiten 918
Vorab online veröffentlicht am 22.02.2021
Schlagwörter colorectal cancer; cancer stem cells; plasticity; cancer stem cell markers; tumor heterogeneity; tumor-organoids; lineage tracing; clonal cooperation; radio-resistance; serial transplantation; therapeutic resistance
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