The plakin family proteins can be therapeutic targets for intrahepatic cholangiocarcinoma

• Project/Area Number: 23592001
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Hyogo Medical University
• Principal Investigator: UYAMA Naoki 兵庫医科大学, 医学部, 講師 (70402873)
• Co-Investigator(Kenkyū-buntansha): FUJIMOTO Jiro 兵庫医科大学, 医学部, 教授 (90199373) ; IIMURO Yuji 兵庫医科大学, 医学部, 教授 (30252018) ; HIRANO Tadamichi 兵庫医科大学, 医学部, 准教授 (90340968) ; SATAKE Makoto 兵庫医科大学, 医学部, 助教 (70399153)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肝内胆管癌 / Plakin / 癌細胞 / 線維芽細胞 / Ｐｌａｋｉｎ / Plakin Family / 癌関連繊維芽細胞 / 増殖能 / 転移能 / 肝内胆管がん / 癌関連線維芽細胞

Outline of Final Research Achievements

Plakin Family consists of cytoskeletal proteins such as plectin , desmoplakin and so on. In this project, we investigated expression of plectin and desmoplakin in human intrahepatic cholangiocarcinoma (ICC) and their fuctions. Immunohistochemistry revealed that these proteins were expressed by cancer cells as well as fibroblasts. In addition, integrin alpha6 and beta4, binding proteins of plectin, and desmocollin desmoglein, binding proteins of desmoplakin, were also expressed by cancer cells. Gene depletion experiments with SiRNA for these proteins revealed that they did not regulate ICC celllines function, such as proliferaion ability, migration ability and ability for activating fibroblas.

Research Products

• [Journal Article] Angiogenesis is crucial for liver regeneration after partial hepatectomy. (2013)
  • Author(s): Uda Y, Hirano T, Son G, Iimuro Y, Uyama N, Yamanaka J, Mori A, Arii S, Fujimoto J.
  • Journal Title: Surgery. Volume: Vol.153、No.1 Issue: 1 Pages: 70-77
  • DOI: 10.1016/j.surg.2012.06.021
  • Peer Reviewed
• [Journal Article] Primary epithelioid hemangioendothelioma of the retroperitoneum: report of a case. (2012)
  • Author(s): Iimuro Y, Nakai N, Asano Y, Uyama N, Suzumura K, Nakai M, Nakasho K, Kashiwagi T, Fujimoto J.
  • Journal Title: Surg Today. Volume: 42(10) Issue: 10 Pages: 1026-1031
  • DOI: 10.1007/s00595-012-0173-1
  • NAID: 10031033044
  • Peer Reviewed
• [Journal Article] 肝胆膵の線維化;研究と診療の最近の進歩 肝臓の線維化:研究の進歩 肝細胞癌,肝内胆管癌の間質を構成する細胞群の特徴 (2012)
  • Author(s): 宇山直樹、飯室勇二, 河田則文, 鈴村和大, 藤元治朗
  • Journal Title: 肝胆膵 Volume: 65(2) Pages: 239-251
  • Peer Reviewed
• [Journal Article] Fascin, a novel marker of human hepatic stellate cells, may regulate their proliferation, migration, and collagen gene expression through the FAK-PI3K-Akt pathway (2012)
  • Author(s): Uyama N, Iimuro Y, Kawada N, Reynaert H, Suzumura K, Hirano T, Kuroda N, Fujimoto J.
  • Journal Title: Laboratory Investigation Volume: 92(1) Issue: 1 Pages: 57-71
  • DOI: 10.1038/labinvest.2011.150
  • Peer Reviewed
• [Journal Article] N-terminal kinase activation by oxidative stress suppresses retinoid signaling through proteasomal degradation of retinoic acid receptor α protein in hepatic cells (2011)
  • Author(s): Hoshikawa Y, Kanki K, Ashla AA, Arakaki Y, Azumi J, Yasui T, Tezuka Y, Matsumi Y, Tsuchiya H, Kurimasa A, Hisatome I, Hirano T, Fujimoto J, Kagechika H, Shomori K, Ito H, Shiota G.
  • Journal Title: Cancer Science Volume: 102(5) Issue: 5 Pages: 934-941
  • DOI: 10.1111/j.1349-7006.2011.01889.x
  • Peer Reviewed
• [Journal Article] Toll-like receptor signaling in liver regeneration, fibrosis and carcinogenesis (2011)
  • Author(s): Seki E, Park E, Fujimoto J.
  • Journal Title: Hepatology Research Volume: 41(7) Issue: 7 Pages: 597-610
  • DOI: 10.1111/j.1872-034x.2011.00822.x
  • NAID: 10031144129
  • Peer Reviewed
• [Presentation] Fascin, an actin bundlling protein, can be a novel marker of human hepatic stellate cells and may regulate functions of Hscs through FAK-PI3K-AKT pathway. (2011)
  • Author(s): Uyama N, Iimuro Y, Kawada N, Reynaert H, Suzumura K, Satake M, Okada T, Hirano T, Kuroda N, Fujimoto J.
  • Organizer: Digestive Disease Week 2011
  • Place of Presentation: Chicago
• [Presentation] Impact of preoperative 3D hepatectomy simulation system for liver resection and transplantation: Application to various kind of liver resection procedure. (2011)
  • Author(s): Fujimoto J, Iimuro Y, Yada A, Kondo Y, Saito S, Sueoka H, Ohashi K.
  • Organizer: 46th Annual Congress of the European Society for Surgical Research
  • Place of Presentation: Aachen
• [Presentation] A novel small molecule inhibitor of FAK inhibits the ability of proliferation and invasion of human cholangiocarcinoma cell lines in vitro. (2011)
  • Author(s): Uyama N, Iimuro Y, Kuroda N, Hirano T, Okada T, Asano Y, Suzumura K, Fujimoto J.
  • Organizer: International Surgical Week ISW 2011
  • Place of Presentation: Yokohama
• [Presentation] 肝内胆管癌組織におけるFAKの発現とその役割. (2011)
  • Author(s): 宇山直樹, 飯室勇二, 近藤祐一, 鈴村和大, 吉田康彦, 佐竹真, 麻野泰包, 岡田敏弘, 平野公通, 黒田暢一, 藤元治朗.
  • Organizer: 第47回日本肝臓学会総会
  • Place of Presentation: 東京
• [Presentation] Expression of fascin in human non-cancerous liver and hepatocellular carcinoma and its function of hepatic stellate cells. (2011)
  • Author(s): Uyama N, Iimuro Y, Kawada N, Reynaert H, Suzumura K, Hirano T, Kuroda N,
  • Organizer: 16th International Symposium on Cells of the Hepatic Sinusoid
  • Place of Presentation: Florence