Research Project
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
The goal of our project is discovery of new molecular-targeted drugs against cancer. To figure out this purpose, in this project, we tried to make clear the molecular mechanism of S1P-PKCzeta signaling with three-dimensional structure level and a role of S1P-PKCzeta signaling in cancer malignancy by internationally collaborating with a researcher who has excellent technique, experience, and circumstance for studying about PKC signaling with molecular structural approach. Then we found that S1P plays a critical role on constant activation of PKCzeta in cancer cells. Also we successfully identified the critical amino acids for interaction between S1P and PKCzeta by combinational approach with in silico docking simulation technique. Finally we showed that the constant activity of S1P-PKCzeta signaling put a brake on nutrient starvation-induced apoptosis in cancer cells.
本研究の成果により、癌の増悪メカニズムの中でも不明な点が多かった、癌細胞がアポトーシスを回避し生存するメカニズムとして、恒常的なS1P-PKCζシグナリングによるアポトーシス抑制機構を新たに同定した。本研究成果のポイントはS1P-PKCζシグナリングの作用機構を立体構造レベルで明らかにした点である。最近ではオーダーメイドがん治療の実現に向けてがんの多様性に合わせた多様な治療手段の開発が求められており、本研究の成果はS1P-PKCζシグナリングの抑制によりアポトーシスのブレーキを外す全く新しいタイプのがん治療法の創出に繋がる。今後は本研究成果の社会実装として新規抗癌剤の創出に向けた研究を進める。
All 2019 2018 2016
All Int'l Joint Research (1 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results, Peer Reviewed: 2 results) Presentation (6 results) (of which Int'l Joint Research: 2 results, Invited: 2 results)
Nature cell biology
Volume: 21 Issue: 3 Pages: 359-371
10.1038/s41556-019-0291-8
Science Signaling
Volume: 12 Issue: 562
10.1126/scisignal.aat6662
