Molecular targets of low-molecular-weight heat shock proteins in hepatocellular carcinoma cell proliferation

• Project/Area Number: 25460989
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Gifu University
• Principal Investigator: KOZAWA Osamu 岐阜大学, 医学(系)研究科(研究院), 教授 (90225417)
• Co-Investigator(Kenkyū-buntansha): OOSAWA Yosuke 岐阜大学, 大学院医学系研究科, 講師 (60447787) ; NISHIWAKI Rie (MATSUSHIMA Rie) 岐阜大学, 大学院医学系研究科, 助教 (90734202)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肝細胞がん / 増殖 / ストレス蛋白質 / 低分子量 / HSP20 / ホスファチジルイノシトール3-キナーゼ / Bax / 肝細胞癌 / リン酸化 / 浸潤 / 転移 / JNK / ＨＳＰ20 / アポトーシス / Ｂａｘ / 細胞増殖 / PI3キナーゼ

Outline of Final Research Achievements

Heat shock protein (HSP) 20, one of the low-molecular-weight HSPs, is recognized to play various functions, such as vasorelaxation. However, its exact roles in cancer proliferation remain to be clarified. While HSP20 is constitutively expressed in various tissues including the liver, we have previously reported that HSP20 overexpression in human hepatocellular carcinoma (HCC) cells represses the cell proliferation. In this study, we investigated the molecular targets of HSP20 in HCC proliferation. Our results strongly suggest that HSP20 interacts with phosphatidylinositol 3-kinase or Bax in HCC cells, resulting in the suppression of cell proliferation.

Research Products

• [Journal Article] Factor Xa inhibitor suppresses the release of phosphorylated HSP27 from collagen-stimulated human platelets: inhibition of HSP27 phosphorylation via p44/p42 MAP kinase. (2016)
  • Author(s): Tsujimoto M, Kuroyanagi G, Matsushima-Nishiwaki R, Kito Y, Enomoto Y, Iida H, Ogura S, Otsuka T, Tokuda H, Kozawa O and Iwama T.
  • Journal Title: PLoS One Volume: 11 Issue: 4 Pages: e0151907-e0151907
  • DOI: 10.1371/journal.pone.0151907
  • Peer Reviewed / Open Access
• [Journal Article] Heat shock protein 20 (HSPB6) regulates apoptosis in human hepatocellular carcinoma cells: Direct association with Bax. (2014)
  • Author(s): Nagasawa T, Matsushima-Nishiwaki R, Toyoda H, Matsuura J, Kumada T, Kozawa O.
  • Journal Title: Oncol Rep. Volume: 32(3) Issue: 3 Pages: 1291-1295
  • DOI: 10.3892/or.2014.3278
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Direct association of heat shock protein 20 (HSPB6) with phosphoinositide 3-kinase (PI3K) in human hepatocellular carcinoma: regulation of the PI3K activity. (2013)
  • Author(s): Matsushima-Nishiwaki R, Kumada T, Nagasawa T, Suzuki M, Yasuda E, Okuda S, Maeda A, Kaneoka Y, Toyoda H, Kozawa O.
  • Journal Title: PLoS One Volume: 8 Issue: 11 Pages: e78440-e78440
  • DOI: 10.1371/journal.pone.0078440
  • Peer Reviewed
• [Remarks] 岐阜大学大学院医学系研究科 分子・構造学講座 薬理病態学分野
  • URL: http://www.med.gifu-u.ac.jp/pharma/index.htm
• [Remarks] 岐阜大学大学院医学系研究科 分子・構造学講座 薬理病態学講座
  • URL: http://www.med.gifu-u.ac.jp/pharma/index.htm
• [Remarks] 岐阜大学大学院医学系研究科 分子・構造学講座 薬理病態学講座
  • URL: http://www.med.gifu-u.ac.jp/pharma/index.htm