Genetic basis of cancer progression by dying tumor cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H06222
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: Enomoto Masato 京都大学, 生命科学研究科, 助教 (00596174)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: がん / 死細胞 / シグナル伝達 / ショウジョウバエ / 細胞間相互作用

Outline of Final Research Achievements

Although it has been recently shown that distinct oncogenic cell clones heterogeneously exist in cancer tissues, it is still poorly understood how tumor-microenvironment causes cancer progression. To elucidate the underlying mechanism, I recapitulated tumor heterogeneity in Drosophila epithelium and genetically analyzed cell-cell interaction of distinct oncogenic cell populations in vivo. In this research, I found that dying Src-activating cells transform surrounding Ras-activating cells to malignant tumors via cell-cell interaction. Furthermore, I also found that malignant Ras-activating cell clones provide metastatic behaviors to surviving Src-activating cells, thereby two oncogenic cell populations mutually invade the adjacent tissues. These findings suggest that two distinct oncogenic cells mutually develop into malignant tumors via cellular cooperation triggered by dying oncogenic cells.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、死にゆく腫瘍細胞がその死と引き換えに周囲の腫瘍細胞に悪性化能を誘発するという新しいがん制御メカニズムを明らかにした。このような細胞死を起点とした細胞間コミュニケーションによるがん制御システムの理解は、新たながん治療戦略や抗がん剤開発の基盤になることが期待できる。