The molecular mechanism of cancer specific cell death induction via novel innate immune signaling

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H06265
• Research Category: Grant-in-Aid for Challenging Research (Pioneering)
• Allocation Type: Single-year Grants
• Research Field: Tumor biology and related fields
• Research Institution: Hokkaido University
• Principal Investigator: Takaoka Akinori 北海道大学, 遺伝子病制御研究所, 教授 (30323611)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Keywords: 自然免疫応答 / RIG-I / インターフェロン / がん細胞 / 細胞死 / 新規キナーゼ / 細胞内局在 / シグナル伝達

Outline of Final Research Achievements

We have been working on the study of innate signaling via pattern recognition mediated receptor for antiviral responses. In this study, we identified a novel innate signaling pathway via cytosolic RNA sensor RIG-I that activates cell death in cancer cells but not normal cells. This novel pathway is different from conventional pathway via MAVS/IPS-1 mediated IFN inducing pathway. Importantly, localization of a kinase protein is not only nucleus but also cytosol in cancer cells while the localization of this is only nucleus in normal cells. RIG-I in cancer cells activate this kinase and activates apoptosis　in cancer cells. Based on our finding that a kinase is localized in cytosol of cancer cells, we propose a novel strategy to modulate ectopic protein for cancer therapy for cancer cells' death.

Free Research Field

分子免疫学

Academic Significance and Societal Importance of the Research Achievements

がん治療において自然免疫療法は、従来の抗癌剤と比べ副作用が少ない利点で期待されている。自然免疫系賦活化(核酸刺激)によって、様々な癌細胞が死滅することが報告されている。しかし、がん細胞の細胞死が一般的に知られる癌細胞内のインターフェロン(interferon;IFN)の作用に依存する説には見解が分かれていた。我々は、核酸によってIFNを誘導するシグナル経路とは異なる新しいがん細胞を死滅させるシグナル経路を同定した。