Heat shock protein 22 (HSPB8) reduces the migration of hepatocellular carcinoma cells through the suppression of the phosphoinositide 3-kinase (PI3K)/AKT pathway

• Project/Area Number: 16K09350
• 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, 大学院医学系研究科, 教授 (90225417)
• Co-Investigator(Kenkyū-buntansha): 安田 一朗 富山大学, 大学院医学薬学研究部(医学), 教授 (00377673)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 肝細胞癌 / 低分子量 / ストレスタンパク質 / HSP22 / 細胞運動 / YAP / HSP20 / HSP27 / ストレス蛋白質 / 肝細胞がん / 増殖 / 転移

Outline of Final Research Achievements

Small heat shock proteins (HSPs) regulate a variety of cell functions. Among them, HSP22 is recognized to be ubiquitously expressed in various tissues. In the present study, we investigated whether HSP22 is implicated in hepatocellular carcinoma cell migration. Our results strongly suggest that HSP22 represses hepatocellular carcinoma progression, especially hepatocellular carcinoma cell migration, by down-regulation of the PI3K/AKT signaling pathway.

Academic Significance and Societal Importance of the Research Achievements

低分子量ストレスタンパク質が具体的にどのような機構で肝がん細胞の増殖、進展を制御しているかについて明らかにした報告は私共のHSP27及びHSP20に関するこれまでの研究以外にはない。本研究においてHSP22が肝がん細胞の遊走を抑制的に制御しているという結果は全く新たな知見である。加えて、HSP22の分子標的がホスファチジルイノシトール3-キナーゼであることも見い出せたことより、低分子量ストレスタンパク質を標的とした新たな肝細胞がん治療法、特に肝がんの転移に対する治療法の確立に大いに資すると考えられた。

Research Products

• [Journal Article] Sphingosine 1-phosphate (S1P) reduces hepatocyte growth factor-induced migration of hepatocellular carcinoma cells via S1P receptor 2. (2018)
  • Author(s): Matsushima-Nishiwaki R, Yamada N, Fukuchi K, Kozawa O.
  • Journal Title: PLoS One. Volume: 13 Issue: 12 Pages: e0209050-e0209050
  • DOI: 10.1371/journal.pone.0209050
  • Peer Reviewed / Open Access
• [Journal Article] Heat shock protein 22 (HSPB8) reduces the migration of hepatocellular carcinoma cells through the suppression of the phosphoinositide 3-kinase (PI3K)/AKT pathway. (2017)
  • Author(s): Matsushima-Nishiwaki R, Toyoda H, Takamatsu R, Yasuda E, Okuda S, Maeda A, Kaneoka Y, Yoshimi N, Kumada T, Kozawa O.
  • Journal Title: Biochim. Biophys Acta-Mol. Basis Dis. Volume: 1863 Issue: 6 Pages: 1629-1639
  • DOI: 10.1016/j.bbadis.2017.04.021
  • Peer Reviewed
• [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
• [Presentation] HSP22はPI3K/AKT経路を阻害し肝癌細胞の遊走を抑制する (2018)
  • Author(s): 西脇理英、吉見直己、小澤 修
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] Phosphorylated HSP20 (HSPB8) regulates TNF-α-induced migration and invasion of hepatocellular carcinoma cells. TNF-α刺激による肝癌細胞遊走および浸潤のリン酸化HSP20 (HSPB8) による抑制 (2016)
  • Author(s): 西脇理英、豊田秀徳、熊田 卓、小澤 修
  • Organizer: 第75回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-06
• [Remarks]
  • URL: http://www.med.gifu-u.ac.jp/pharma/index.htm
• [Remarks] 岐阜大学医学部薬理病態学
  • URL: http://www.med.gifu-u.ac.jp/pharma/index.htm
• [Remarks]
  • URL: http://www.med.gifu-u.ac.jp/pharma/index.htm