Novel therapeutic strategy targeting pancreatic cancer stem cell-niche

• Project/Area Number: 23390194
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tohoku University
• Principal Investigator: SHIMOSEGAWA Tooru 東北大学, 大学病院, 教授 (90226275)
• Co-Investigator(Kenkyū-buntansha): MASAMUNE Atsushi 東北大学, 医学系研究科, 准教授 (90312579) ; SATOH Kennichi 宮城県立がんセンター, がん幹細胞研究部, 部長 (10282055) ; HAMADA Shin 東北大学, 医学系研究科, 助教 (20451560)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2012: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2011: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: microRNA / cancer stem cell / EMT / マイクロRNA / CDCP1 / 膵癌

Research Abstract

We performed a comprehensive analysis to identify an important regulator of cancer stem cell-related phenotype and a novel marker of pancreatic cancer stem cell. miR-197 was highly expressed in pancreatic cancer tissue compared with IPMN, and this microRNA had an epithelial to mesenchymal transition (EMT)-promoting role in cancer cells. miR-197 directly targeted p120 catenin, which was important for the maintenance of epithelial phenotypes. A membrane protein CDCP1 was highly expressed in pancreatic cancer cells, whose knockdown attenuated the cancer stem cell-related phenotypes such as EMT or spheroid formation. Furthermore, we confirmed that the expression of CDCP1 was regulated by BMP4/ERK pathway in pancreatic cancer cells. These data would lead to the identification of novel therapeutic targets that could eliminate cancer stem cells.

Research Products

• [Journal Article] CUB-domain containing protein 1 represses the epithelial phenotype of pancreatic cancer cells (2014)
  • Author(s): Miura S, Hamada S, Masamune A, Satoh K, Shimosegawa T
  • Journal Title: Exp Cell Res Volume: 321(2) Issue: 2 Pages: 209-218
  • DOI: 10.1016/j.yexcr.2013.12.019
  • Peer Reviewed
• [Journal Article] MiR-365 induces gemcitabine resistance in pancreatic cancer cells by targeting the adaptor protein SHC1 and pro-apoptotic regulator BAX (2014)
  • Author(s): Hamada S, Masamune A, Miura S, Satoh K, Shimosegawa T
  • Journal Title: Cell Signal Volume: 26(2) Issue: 2 Pages: 179-185
  • DOI: 10.1016/j.cellsig.2013.11.003
  • Peer Reviewed
• [Journal Article] Inflammation and pancreatic cancer: disease promoter and new therapeutic target. (2014)
  • Author(s): Hamada S, Masamune A, Shimosegawa T.
  • Journal Title: J Gastroenterol. Volume: 49 Issue: 4 Pages: 605-617
  • DOI: 10.1007/s00535-013-0915-x
  • Peer Reviewed
• [Journal Article] miR-197 induces epithelialmesenchymal transition in pancreatic cancer cells by targeting p120 catenin. J Cell Physiol (2013)
  • Author(s): Hamada S, et al
  • Journal Title: J Cell Physiol Volume: 228(6) Issue: 6 Pages: 1255-63
  • DOI: 10.1002/jcp.24280
  • Peer Reviewed
• [Journal Article] Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells (2012)
  • Author(s): Hamada S, Masamune A, Takikawa T, Suzuki N, Kikuta K, Hirota M, Hamada H, Kobune M, Satoh K, Shimosegawa T
  • Journal Title: Biochem Biophys Res Commun Volume: 421(2) Issue: 2 Pages: 349-354
  • DOI: 10.1016/j.bbrc.2012.04.014
  • Peer Reviewed
• [Journal Article] MiR-126 acts as a tumor suppressor in pancreatic cancer cells via the regulation of ADAM9 (2012)
  • Author(s): Hamada S, Satoh K, Fujibuchi W, Hirota M, Kanno A, Unno J, Masamune A, Kikuta K, Kume K, Shimosegawa T
  • Journal Title: Mol Cancer Res Volume: 10(1) Issue: 1 Pages: 3-10
  • DOI: 10.1158/1541-7786.mcr-11-0272
  • Peer Reviewed
• [Journal Article] Biomarkers of pancreatic cancer (2011)
  • Author(s): Hamada S, Shimosegawa T
  • Journal Title: Pancreatology Volume: 11 Suppl 2 Issue: 2 Pages: 14-19
  • DOI: 10.1159/000323479
  • Peer Reviewed
• [Presentation] 浸潤性膵癌特異的oncomiR であるmiR-197 はVDAC1 発現を制御し好気的解糖を促進する (2013)
  • Author(s): 濱田晋, 佐藤賢一, 正宗淳, 菅野敦, 菊田和宏, 粂潔, 廣田衛久, 下瀬川徹
  • Organizer: 第44回膵臓学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2013-07-25
• [Presentation] Identification of inflammatory signal-stimulating microRNA in pancreatic duct cell carcinoma (2013)
  • Author(s): Hamada S, Satoh K, Masamune A, and Shimosegawa T
  • Organizer: JSGE-ITC 2013
  • Place of Presentation: 鹿児島
  • Year and Date: 2013-03-23
• [Presentation] MiR-365 indirectly regulates drug resistance-related molecule Aryl hydrocarbon receptor nuclear translocator expression in pancreatic ductal adenocarcinoma cells. (2013)
  • Author(s): Hamada S, Satoh K, Masamune A, Kanno A, Kikuta K, Kume K, Unno J, Hirota M and Shimosegawa T.
  • Organizer: DDW2013
  • Place of Presentation: Orland, FL, USA
• [Presentation] CUB-domain containing protein-1 is a novel marker of epithelial-mesenchymal transition (2013)
  • Author(s): Miura S, HamadaS, Masamune A, Shimosegawa T.
  • Organizer: DDW2013
  • Place of Presentation: Orland, FL, USA
• [Presentation] Identification of invasion-related microRNAs in pancreatic cancer by comprehensive analysis (2012)
  • Author(s): Hamada S, Satoh K, Hirota M, Kanno A, Masamune A, Kikuta K, Kume K, Unno J and Shimosegawa T
  • Organizer: UEGW 2012 Amsterdam
  • Year and Date: 2012-10-23
• [Presentation] miR-197 は膵癌細胞のEMT 誘導因子であり (2012)
  • Author(s): 濱田晋, 佐藤賢一, 三浦晋, 廣田衛久, 菅野敦, 正宗淳, 菊田和宏, 粂潔, 海野純, 江川新一, 元井冬彦, 海野倫明, 下瀬川徹
  • Organizer: p120 catenin 発現を制御するJDDW 2012
  • Place of Presentation: 神戸
  • Year and Date: 2012-10-10
• [Presentation] Identification of invasion-related microRNAs in pancreatic cancer by comprehensive analysis. (2012)
  • Author(s): Shin Hamada, Kennichi Satoh, Morihisa Hirota, Atsushi Kanno, Atsushi Masamune, Kazuhiro Kikuta, Kiyoshi Kume, Jun Unno and Tooru Shimosegawa.
  • Organizer: UEGW 2012
  • Place of Presentation: Amsterdam、オランダ
• [Presentation] miR-197は膵癌細胞のEMT誘導因子であり、p120 catenin発現を制御する (2012)
  • Author(s): 濱田晋 佐藤賢一 三浦晋 廣田衛久 菅野敦 正宗淳 菊田和宏 粂潔 海野純 江川新一 元井冬彦 海野倫明 下瀬川徹
  • Organizer: JDDW 2012
  • Place of Presentation: 神戸
• [Presentation] 膵癌特異的なマイクロRNA発現プロファイル解析からの悪性化因子の同定 (2011)
  • Author(s): 濱田晋, 佐藤賢一, 下瀬川徹
  • Organizer: JDDW 2011
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-23