Krt19+/Lgr5- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine

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

doi:10.1016/j.stem.2015.04.013

Krt19⁺/Lgr5^- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine

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

Radiation Oncology

Research output: Contribution to journal › Article › peer-review

147 Scopus citations

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.

Original language	English (US)
Pages (from-to)	627-638
Number of pages	12
Journal	Cell Stem Cell
Volume	16
Issue number	6
DOIs	https://doi.org/10.1016/j.stem.2015.04.013
State	Published - Jun 4 2015

ASJC Scopus subject areas

Molecular Medicine
Genetics
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.stem.2015.04.013

Cite this

Asfaha, S., Hayakawa, Y., Muley, A., Stokes, S., Graham, T. A., Ericksen, R. E., Westphalen, C. B., Von Burstin, J., Mastracci, T. L., Worthley, D. L., Guha, C., Quante, M., Rustgi, A. K., & Wang, T. C. (2015). Krt19⁺/Lgr5^- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine. Cell Stem Cell, 16(6), 627-638. https://doi.org/10.1016/j.stem.2015.04.013

@article{d44d3d55a0e0406fbeade14547851036,

title = "Krt19+/Lgr5- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine",

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.",

author = "Samuel Asfaha and Yoku Hayakawa and Ashlesha Muley and Sarah Stokes and Graham, {Trevor A.} and Ericksen, {Russell E.} and Westphalen, {Christoph B.} and {Von Burstin}, Johannes and Mastracci, {Teresa L.} and Worthley, {Daniel L.} and Chandhan Guha and Michael Quante and Rustgi, {Anil K.} and Wang, {Timothy C.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = jun,

day = "4",

doi = "10.1016/j.stem.2015.04.013",

language = "English (US)",

volume = "16",

pages = "627--638",

journal = "Cell Stem Cell",

issn = "1934-5909",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Krt19+/Lgr5- Cells Are Radioresistant Cancer-Initiating Stem Cells in the Colon and Intestine

AU - Asfaha, Samuel

AU - Hayakawa, Yoku

AU - Muley, Ashlesha

AU - Stokes, Sarah

AU - Graham, Trevor A.

AU - Ericksen, Russell E.

AU - Westphalen, Christoph B.

AU - Von Burstin, Johannes

AU - Mastracci, Teresa L.

AU - Worthley, Daniel L.

AU - Guha, Chandhan

AU - Quante, Michael

AU - Rustgi, Anil K.

AU - Wang, Timothy C.

PY - 2015/6/4

Y1 - 2015/6/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84947806812&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84947806812&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2015.04.013

DO - 10.1016/j.stem.2015.04.013

M3 - Article

C2 - 26046762

AN - SCOPUS:84947806812

SN - 1934-5909

VL - 16

SP - 627

EP - 638

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 6

ER -