Identification of molecular target protein of small heat shock proteins and analysis of their functional regulatory system

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08283
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Gifu University
• Principal Investigator: Nishiwaki Rie 岐阜大学, 大学院医学系研究科, 助教 (90734202)
• Co-Investigator(Kenkyū-buntansha): 高井 光治 岐阜大学, 大学院医学系研究科, 特任教授 (70402196) ; 小澤 修 岐阜大学, 大学院医学系研究科, 教授 (90225417)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ストレスタンパク質 / 低分子量 / 肝細胞癌 / 細胞運動

Outline of Final Research Achievements

Small heat shock proteins (HSPBs) regulate a variety of cellular functions. We have previously reported that HSP20, HSP22 and HSP27 are highly expressed in hepatocellular carcinoma (HCC) and that each HSP suppresses the progression of HCC. HSPBs are known to form protein complexes with various molecular target proteins and regulate them. In the present study, we investigated the target proteins to which HSPB binds in HCC. HSP27/HSP20 and HSP27/HSP22 complexes were observed in both HSPB6-overexpressing human HCC derived HuH-7 cells and resected human HCC tumor tissues, but not the HSP20/HSP22 complex. The presence of the HSPB complexes in HCC tissue was inversely corelated with the progression of HCC. Our results strongly suggest that the formation of HSPB complexes plays a suppressive role in HCC progression.

Free Research Field

肝臓学　腫瘍生物学　細胞生物学　薬理学

Academic Significance and Societal Importance of the Research Achievements

低分子量ストレス蛋白質（HSPB）による肝細胞癌の進展の制御については、私共が世界に先んじてその機構の詳細の検討を行っている。本研究において私共が見出した、肝癌細胞内においてHSP27がHSP20およびHSP22を標的分子として各々と独立に複合体を形成するという結果に加え、これらHSPB複合体の存在と肝細胞癌の進展との間には、分化度、大きさ、ステージ、脈管浸潤において逆相関の関係があるという結果は、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癌の治療法の確立に大いに資すると考えられた。