Investigation of the HSF1 signaling pathway as the molecular targeted therapies for hepatocellular carcinoma.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460982
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Yokohama City University
• Principal Investigator: Makoto Chuma 横浜市立大学, 附属市民総合医療センター, 准教授 (30360910)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肝癌 / 分子標的治療 / HSF1

Outline of Final Research Achievements

HSF1, a major transactivator of stress responses, has been implicated in carcinogenesis in various organs. We investigated to clarify the functional role of HSF1 in HCC. Tumorigenicity was significantly reduced in orthotopic mice with HSF1-KD cells compared to those with HSF1-control cells. Reduced tumorigenesis in HSF1-KD cells appeared attributable to increased apoptosis and decreased proliferation. Tumor necrosis factor α-induced apoptosis was increased in HSF1-KD cells and HSF1-/- mouse. Decreased expression of IKKγ, a positive regulator of nuclear factor κB, was also observed in HSF1-KD cells and HSF1-/- mouse hepatocytes. Clinicopathological analysis demonstrated frequent overexpression of HSF1 in human HCCs. Significant correlations between HSF1 protein levels and prognosis were also observed. In summary, these results identify a mechanistic link between HSF1 and liver tumorigenesis and may provide as a potential molecular target for the development of anti-HCC therapies.

Free Research Field

消化器病学