DCLK1 facilitates intestinal tumor growth via enhancing pluripotency and epithelial mesenchymal transition

作者: Parthasarathy Chandrakesan , Nathaniel Weygant , Randal May , Dongfeng Qu , Harisha R. Chinthalapally

DOI: 10.18632/ONCOTARGET.2393

关键词: Stem cellEpithelial–mesenchymal transitionBiologyCancer researchIntestinal epitheliumCarcinogenesisColorectal cancerIntestinal mucosaCancerAdenocarcinoma

摘要: // Parthasarathy Chandrakesan 1 , 2 Nathaniel Weygant Randal May 4 Dongfeng Qu Harisha R. Chinthalapally Sripathi M. Sureban Naushad Ali Stan A. Lightfoot 3 Shahid Umar 5 Courtney W. Houchen Department of Medicine, University Oklahoma Health Sciences center, City, OK 73104, USA OU Cancer Institute, Pathology, Center, Veterans Affairs Medical Molecular and Integrative Physiology, Kansas KS, Correspondence to Houchen, M.D. e-mail: Courtney-houchen@ouhsc.edu Key words: Dclk1; self-renewal; pluripotency; EMT; miRNAs; tumorigenesis Received: August 18, 2014      Accepted: 21, Published: September 02, 2014 ABSTRACT Doublecortin-like kinase (Dclk1) is overexpressed in many cancers including colorectal cancer (CRC) andit specifically marks intestinal tumor stem cells. However, the role Dclk1 Apc mutant conditions still poorly understood. We demonstrate that expression Dclk1+ cells are significantly increased epithelium elderly Min /+ mice compared young wild type mice. Intestinal epithelial pluripotency, self-renewing ability, EMT. Furthermore, miRNAs dysregulated, onco-miRNAs with decreased suppressor miRNAs. In support these findings, knockdown attenuates adenomas adenocarcinoma by decreasing EMT indicating overexpression facilitates tumorigenesis. Knocking down weakens Dclk1-dependent processes for This study demonstrates critically involved facilitating enhancing pluripotency factors tumors it also provides a potential therapeutic target treatment cancer.

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