The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Long-lived intestinal tuft cells serve as colon cancer–initiating cells
Open accessAbstract
Doublecortin-like kinase 1 protein (DCLK1) is a gastrointestinal tuft cell marker that has been proposed to identify quiescent and tumor growth-sustaining stem cells. DCLK1⁺ tuft cells are increased in inflammation-induced carcinogenesis; however, the role of these cells within the gastrointestinal epithelium and their potential as cancer-initiating cells are poorly understood. Here, using a BAC-CreERT-dependent genetic lineage-tracing strategy, we determined that a subpopulation of DCLK1⁺ cells is extremely long lived and possesses rare stem cell abilities. Moreover, genetic ablation of Dclk1 revealed that DCLK1⁺ tuft cells contribute to recovery following intestinal and colonic injury. Surprisingly, conditional knockdown of the Wnt regulator APC in DCLK1⁺ cells was not sufficient to drive colonic carcinogenesis under normal conditions; however, dextran sodium sulfate-induced (DSS-induced) colitis promoted the development of poorly differentiated colonic adenocarcinoma in mice lacking APC in DCLK1⁺ cells. Importantly, colonic tumor formation occurred even when colitis onset was delayed for up to 3 months after induced APC loss in DCLK1⁺ cells. Thus, our data define an intestinal DCLK1⁺ tuft cell population that is long lived, quiescent, and important for intestinal homeostasis and regeneration. Long-lived DCLK1⁺ cells maintain quiescence even following oncogenic mutation, but are activated by tissue injury and can serve to initiate colon cancer.
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Metadata
- Authors
- Westphalen, C. B., Asfaha, S., Hayakawa, Y., Takemoto, Y., Lukin, D. J., Nuber, A. H., Brandtner, A., Setlik, W., Remotti, H., Muley, A., Chen, X., May, R., Houchen, C. W., Fox, J. G., Gershon, M. D., Quante, M., & Wang, T. C.
- Venue
- Journal of Clinical Investigation
- Published
- 2014-02-03
- Volume
- 124
- Issue
- 3
- Pages
- 1283-1295
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2014911043
- Cited by
- 389
- References
- 7
- FWCI
- 15.80
- Type
- journal article
- Language
- en
- Open access
- green
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- Westphalen, C. B., Asfaha, S., Hayakawa, Y., Takemoto, Y., Lukin, D. J., Nuber, A. H., Brandtner, A., Setlik, W., Remotti, H., Muley, A., Chen, X., May, R., Houchen, C. W., Fox, J. G., Gershon, M. D., Quante, M., & Wang, T. C. (2014). Long-lived intestinal tuft cells serve as colon cancer–initiating cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci73434
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