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Type: Journal article
Title: Krt19⁺/Lgr5⁻ cells are radioresistant cancer-initiating stem cells in the colon and intestine
Other Titles: Krt19(+)/Lgr5(-) cells are radioresistant cancer-initiating stem cells in the colon and intestine
Author: Asfaha, S.
Hayakawa, Y.
Muley, A.
Stokes, S.
Graham, T.
Ericksen, R.
Westphalen, C.
Von Burstin, J.
Mastracci, T.
Worthley, D.
Guha, C.
Quante, M.
Rustgi, A.
Wang, T.
Citation: Cell Stem Cell, 2015; 16(6):627-638
Issue Date: 2015
ISSN: 1934-5909
Statement of
Samuel 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
Abstract: Epithelium 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.
Keywords: Neoplastic Stem Cells
Rights: © 2015 Elsevier Inc.
RMID: 0030039082
DOI: 10.1016/j.stem.2015.04.013
Appears in Collections:Physics publications

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