DCLK1 regulates stemness feature in neuroendocrine tumors.

• Project/Area Number: 15K19355
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kurume University
• Principal Investigator: Ikezono Yu 久留米大学, 医学部, 助教 (10461419)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: DCLK1 / NET / FAK / SLUG / EMT / 神経内分泌腫瘍 / 癌幹細胞

Outline of Final Research Achievements

DCLK1 is a marker for intestinal and pancreatic cancer stem cells. This study was conducted to assess DCLK1 expression levels in pancreatic neuroendocrine tumor (PNET) tissues and to explore the roles of this molecule in PNET. Immunohistochemically, all PNET tissues highly and diffusely expressed DCLK1. A DCLK1-overexpressing PNET cell(QGP1-DCLK1) exhibited EMT-related gene signatures, and upregulation of Slug, N-Cadherin, and Vimentin was validated by real-time PCR and immunoblotting. QGP1-DCLK1 cells had increased cell migration and proliferation. The factors involved in the formation of the fast-growing tumors included p-FAK (on Tyr925), p-ERK1/2 and p-AKT. In conclusion, robust and ubiquitous expression of DCLK1 was demonstrated in human PNET tissues and cells. DCLK1 characterized the PNET cell behavior, inducing p-FAK/ SLUG-mediated EMT. These findings suggest the possibility of developing novel therapeutic strategies against PNETs by targeting DCLK1.

Research Products

• [Journal Article] Pancreatic Neuroendocrine Tumors and EMT Behavior Are Driven by the CSC Marker DCLK1 (2017)
  • Author(s): Yu Ikezono
  • Journal Title: Molecular Cancer Research Volume: 不明 Issue: 6 Pages: 744-752
  • DOI: 10.1158/1541-7786.mcr-16-0285
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors. (2015)
  • Author(s): Ikezono YU, Koga H, Abe M, Akiba J, Kawahara A, Yoshida T, Nakamura T, Iwamoto H, Yano H, Kage M, Sata M, Tsuruta O, Torimura T.
  • Journal Title: Oncology Letters Volume: 10 Issue: 4 Pages: 2015-2020
  • DOI: 10.3892/ol.2015.3513
  • Peer Reviewed / Open Access
• [Presentation] 膵神経内分泌腫瘍において幹細胞マーカーDCLK1はTyr925FAKを介し、腫瘍増殖・遊走を促進させる (2016)
  • Author(s): 池園 友
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Presentation] DCLK1 promotes tumor growth and invasion through Slug-mediated epithelial-mesenchymal transition in pancreatic neuroendocrine tumors (2016)
  • Author(s): Yu Ikezono
  • Organizer: AACR2016
  • Place of Presentation: New Orleans, Louisiana, USA
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] The putative cancer stem cell marker DCLK1 is highly expressed in pancreatic neuroendocrine tumors and induces epithelial-mesenchymal transition (2015)
  • Author(s): Yu Ikezono
  • Organizer: UEGW2015
  • Place of Presentation: Carrer del Foc, 35, Barcelona, Spain
  • Year and Date: 2015-10-24
  • Int'l Joint Research
• [Presentation] 膵神経内分泌腫瘍における癌幹細胞マーカーDclk1の機能解析 (2015)
  • Author(s): 池園 友
  • Organizer: JDDW2015
  • Place of Presentation: 東京
  • Year and Date: 2015-10-08