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DCLK1 facilitates intestinal tumor growth via enhancing pluripotency and epithelial mesenchymal transition.
- Source :
-
Oncotarget [Oncotarget] 2014 Oct 15; Vol. 5 (19), pp. 9269-80. - Publication Year :
- 2014
-
Abstract
- Doublecortin-like kinase 1 (Dclk1) is overexpressed in many cancers including colorectal cancer (CRC) andit specifically marks intestinal tumor stem cells. However, the role of Dclk1 in intestinal tumorigenesis in Apc mutant conditions is still poorly understood. We demonstrate that Dclk1 expression and Dclk1+ cells are significantly increased in the intestinal epithelium of elderly ApcMin/+ mice compared to young ApcMin/+ mice and wild type mice. Intestinal epithelial cells of ApcMin/+ mice demonstrate increased pluripotency, self-renewing ability, and EMT. Furthermore, miRNAs are dysregulated, expression of onco-miRNAs are significantly increased with decreased tumor suppressor miRNAs. In support of these findings, knockdown of Dclk1 in elderly ApcMin/+ mice attenuates intestinal adenomas and adenocarcinoma by decreasing pluripotency, EMT and onco-miRNAs indicating that Dclk1 overexpression facilitates intestinal tumorigenesis. Knocking down Dclk1 weakens Dclk1-dependent intestinal processes for tumorigenesis. This study demonstrates that Dclk1 is critically involved in facilitating intestinal tumorigenesis by enhancing pluripotency and EMT factors in Apc mutant intestinal tumors and it also provides a potential therapeutic target for the treatment of colorectal cancer.
- Subjects :
- Adenocarcinoma genetics
Adenoma genetics
Animals
Cell Transformation, Neoplastic genetics
Doublecortin-Like Kinases
Epithelial Cells pathology
Intestinal Mucosa metabolism
Intestinal Neoplasms genetics
Intestines cytology
Mice
Mice, Inbred C57BL
Mice, Transgenic
MicroRNAs genetics
Protein Serine-Threonine Kinases biosynthesis
RNA Interference
RNA, Small Interfering
Spheroids, Cellular
Tumor Cells, Cultured
Adenomatous Polyposis Coli Protein genetics
Epithelial-Mesenchymal Transition genetics
Intestinal Neoplasms pathology
Neoplastic Stem Cells pathology
Protein Serine-Threonine Kinases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 5
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 25211188
- Full Text :
- https://doi.org/10.18632/oncotarget.2393