The role of cGAS-STING pathway in cancer maintenance and metastasis

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07759
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Nippon Medical School
• Principal Investigator: Uehara Ikuno 日本医科大学, 先端医学研究所, 助教 (50434139)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: cGAS-STING経路 / IFN-α/β / sphere / がん幹細胞

Outline of Final Research Achievements

The purpose of this study was to clarify the mechanism of how the c-GAS-STING pathway, which is activated by anticancer drugs and radiotherapy, is involved in carcinogenesis and cancer stem cell maintenance. We found that IFN-α/β produced by activation of the cGAS-STING pathway suppresses cancer cell proliferation but promotes oGlcNAc modification, which is involved in cancer stem cell maintenance, and enhances PD-L1 expression. Furthermore, inflammatory cytokines involved in SASP, which are simultaneously produced by activation of the c-GAS-STING pathway, are also involved in the maintenance of cancer stem cells, and the STING inhibitor H-151, which blocks this pathway, was found to be a candidate therapeutic for cancer stem cell suppression.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

がんの再発・転移を抑制することは、がんの完治をもたらすが、実際に放射線治療や抗がん剤治療を行なっても、今のところ再発・転移を抑制することはできない。本研究では、放射線刺激や抗がん剤によるDNA損傷によって活性化される、cGAS-STING経路を介して産生されるIFN-α/βや炎症性サイトカインが、がん幹細胞の維持やがん転移に関与していることがわかり、さらにSTING阻害剤でcGAS-STING経路を抑制することにより、がん幹細胞の生存を下げる結果を見出した。今後、抗がん剤や放射線治療とSTING阻害剤の併用により、がんの転移再発を抑制できる可能性がある点で、非常に意義があると思われる。