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Krt19⁺/Lgr5⁻ cells are radioresistant cancer-initiating stem cells in the colon and intestine

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dc.contributor.authorAsfaha, S.
dc.contributor.authorHayakawa, Y.
dc.contributor.authorMuley, A.
dc.contributor.authorStokes, S.
dc.contributor.authorGraham, T.
dc.contributor.authorEricksen, R.
dc.contributor.authorWestphalen, C.
dc.contributor.authorVon Burstin, J.
dc.contributor.authorMastracci, T.
dc.contributor.authorWorthley, D.
dc.contributor.authorGuha, C.
dc.contributor.authorQuante, M.
dc.contributor.authorRustgi, A.
dc.contributor.authorWang, T.
dc.date.issued2015
dc.description.abstractEpithelium of the colon and intestine are renewed every 3 days. In the intestine there are at least two principal stem cell pools. The first contains rapid cycling crypt-based columnar (CBC) Lgr5(+) cells, and the second is composed of slower cycling Bmi1-expressing cells at the +4 position above the crypt base. In the colon, however, the identification of Lgr5(-) stem cell pools has proven more challenging. Here, we demonstrate that the intermediate filament keratin-19 (Krt19) marks long-lived, radiation-resistant cells above the crypt base that generate Lgr5(+) CBCs in the colon and intestine. In colorectal cancer models, Krt19(+) cancer-initiating cells are also radioresistant, while Lgr5(+) stem cells are radiosensitive. Moreover, Lgr5(+) stem cells are dispensable in both the normal and neoplastic colonic epithelium, as ablation of Lgr5(+) stem cells results in their regeneration from Krt19-expressing cells. Thus, Krt19(+) stem cells are a discrete target relevant for cancer therapy.
dc.description.statementofresponsibilitySamuel Asfaha, Yoku Hayakawa, Ashlesha Muley, Sarah Stokes, Trevor A. Graham, Russell E. Ericksen, Christoph B. Westphalen, Johannes von Burstin, Teresa L. Mastracci, Daniel L. Worthley, Chandhan Guha, Michael Quante, Anil K. Rustgi, Timothy C. Wang
dc.identifier.citationCell Stem Cell, 2015; 16(6):627-638
dc.identifier.doi10.1016/j.stem.2015.04.013
dc.identifier.issn1934-5909
dc.identifier.issn1875-9777
dc.identifier.orcidWorthley, D. [0000-0003-0374-9124]
dc.identifier.urihttp://hdl.handle.net/2440/105453
dc.language.isoen
dc.publisherElsevier BV
dc.rights© 2015 Elsevier Inc.
dc.source.urihttps://doi.org/10.1016/j.stem.2015.04.013
dc.subjectNeoplastic Stem Cells
dc.titleKrt19⁺/Lgr5⁻ cells are radioresistant cancer-initiating stem cells in the colon and intestine
dc.title.alternativeKrt19(+)/Lgr5(-) cells are radioresistant cancer-initiating stem cells in the colon and intestine
dc.typeJournal article
pubs.publication-statusPublished

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