DCLK1 Facilitates Intestinal Tumor Growth Via Enhancing Pluripotency and Epithelial Mesenchymal Transition

Overview

Journal Oncotarget

Specialty Oncology

Date 2014 Sep 12

PMID 25211188

Citations 56

Authors

Parthasarathy Chandrakesan

Nathaniel Weygant

Randal May

Dongfeng Qu

Harisha R Chinthalapally

Sripathi M Sureban

Naushad Ali

Stan A Lightfoot

Shahid Umar

Courtney W Houchen

Affiliations

Soon will be listed here.

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.

Citing Articles

From Inflammation to Oncogenesis: Tracing Serum DCLK1 and miRNA Signatures in Chronic Liver Diseases.

Moore L, Qu D, Sureban S, Mitchell S, Pitts K, Cooper N Int J Mol Sci. 2024; 25(12).

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Brain-derived neurotrophic factor - a key player in the gastrointestinal system.

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Epigenetic Landscape and Therapeutic Implication of Gene Isoforms of Doublecortin-Like Kinase 1 for Cancer Stem Cells.

Moore L, Houchen C Int J Mol Sci. 2023; 24(22).

PMID: 38003596 PMC: 10671580. DOI: 10.3390/ijms242216407.

Intestinal Tuft Cells: Morphology, Function, and Implications for Human Health.

Silverman J, Vega P, Tyska M, Lau K Annu Rev Physiol. 2023; 86:479-504.

PMID: 37863104 PMC: 11193883. DOI: 10.1146/annurev-physiol-042022-030310.

Targeting doublecortin-like kinase 1 reveals a novel strategy to circumvent chemoresistance and metastasis in ovarian cancer.

Dogra S, Elayapillai S, Qu D, Pitts K, Filatenkov A, Houchen C Cancer Lett. 2023; 578:216437.

PMID: 37838282 PMC: 10872611. DOI: 10.1016/j.canlet.2023.216437.

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