title: DCLK1 facilitates intestinal tumor growth via enhancing pluripotency and epithelial mesenchymal transition.
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.
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences center, Oklahoma City, OK 73104, USA. OU Cancer Institute, University of Oklahoma Health Sciences center, Oklahoma City, OK 73104, USA.
authors.forename: Parthasarathy
authors.initials: P
authors.lastname: Chandrakesan
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences center, Oklahoma City, OK 73104, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Weygant
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences center, Oklahoma City, OK 73104, USA. Department of Veterans Affairs Medical Center, Oklahoma City, OK 73104, USA.
authors.forename: Randal
authors.initials: R
authors.lastname: May
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences center, Oklahoma City, OK 73104, USA. OU Cancer Institute, University of Oklahoma Health Sciences center, Oklahoma City, OK 73104, USA.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Qu
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences center, Oklahoma City, OK 73104, USA.
authors.forename: Harisha R
authors.initials: HR
authors.lastname: Chinthalapally
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences center, Oklahoma City, OK 73104, USA. Department of Veterans Affairs Medical Center, Oklahoma City, OK 73104, USA.
authors.forename: Sripathi M
authors.initials: SM
authors.lastname: Sureban
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences center, Oklahoma City, OK 73104, USA.
authors.forename: Naushad
authors.initials: N
authors.lastname: Ali
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Stan A
authors.initials: SA
authors.lastname: Lightfoot
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Shahid
authors.initials: S
authors.lastname: Umar
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences center, Oklahoma City, OK 73104, USA. OU Cancer Institute, University of Oklahoma Health Sciences center, Oklahoma City, OK 73104, USA. Department of Veterans Affairs Medical Center, Oklahoma City, OK 73104, USA.
authors.forename: Courtney W
authors.initials: CW
authors.lastname: Houchen
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000236:Adenoma / Q000235:genetics; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D000089742:Doublecortin-Like Kinases; D004847:Epithelial Cells / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology*; D007422:Intestines / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D018874:Spheroids, Cellular; D014407:Tumor Cells, Cultured
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D035683:MicroRNAs; D034741:RNA, Small Interfering; D000089742:Doublecortin-Like Kinases; C485525:Dclk1 protein, mouse; D017346:Protein Serine-Threonine Kinases