The genetic dissection of cell competition in tumor microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19257
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: Nagoya University
• Principal Investigator: Ohsawa Shizue 名古屋大学, 理学研究科, 教授 (80515065)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 細胞競合 / スーパーコンペティション / がん / ショウジョウバエ

Outline of Final Research Achievements

There are growing evidence showing that tumor growth and progression is achieved by “supercompetition”, a phenomenon in which oncogenic cells (“Winners”) competitively proliferate by eliminating neighboring cells (“Losers”) from the tissue. In this study, by using the powerful Drosophila model system, we conducted two types of genetic screens for identifying factors that are crucial for super competition. We found that mutations in autophagy-related genes in neighboring cells strongly suppressed supercompetition of oncogenic cells mutant for a Hippo pathway component fat. Genetic analyses revealed that fat mutant clones eliminate neighboring cells by non-autonomous Autophagy, which lead to induction of cell death. In addition, we identified a novel gene that are crucial for supercompetition. Subsequent genetic and live imaging analyses for elucidating the role of the identified novel gene would contribute to understand the mechanism of tumor development through supercompetition.

Free Research Field

発生遺伝学

Academic Significance and Societal Importance of the Research Achievements

がん原性細胞が正常細胞を駆逐しながらその領地を拡大する“スーパーコンペティション”は、がん促進を担う重要なファクターとして近年大きく着目されているが、その分子実体はほとんど分かっていなかった。本研究において、ショウジョウバエをモデルとした網羅的な遺伝学的解析を実施することで、組織に生じたがん原性細胞が、周辺細胞に対してオートファジーを介した細胞死を誘導するという新規メカニズムが明らかとなった。今後、オートファジーが誘導されるメカニズムをさらに解析し、進化的保存性を検証していくことで、正常細胞をターゲットとしたがん治療の開発につながる可能性が期待される。