Mechanism of tumor-suppressive cell competition in flies

Cancer Science
Tatsushi Igaki, Tatsushi Igaki

Abstract

Oncogenic mutations often trigger anti-tumor cellular response such as induction of apoptosis or cellular senescence. Studies in the last decade have identified the presence of the third guardian against mutation-induced tumorigenesis, namely 'cell competition'. Cell competition is a context-dependent cell elimination whereby cells with higher fitness eliminate neighboring cells with lower fitness by inducing cell death. While oncogene-induced apoptosis or oncogene-induced senescence acts as a cell-autonomous tumor suppressor, cell competition protects tissue from tumorigenesis via cell-cell communication. For instance, in Drosophila epithelium, oncogenic cells with cell-polarity mutations overproliferate and develop into tumors on their own but are eliminated from the tissue when surrounded by wild-type cells. Genetic studies in flies have unraveled that such tumor-suppressive cell competition is regulated by at least three mechanisms: direct cell-cell interaction between polarity-deficient cells and wild-type cells, secreted factors from epithelial cells, and systemic factors from distant organs. Molecular manipulation of tumor-suppressive cell competition could provide a novel therapeutic strategy against human cancers.

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Citations

Aug 11, 2021·Biochemical and Biophysical Research Communications·Sachi SunagaHiroshi Nishina
Aug 28, 2021·International Journal of Molecular Sciences·Caitlin Hounsell, Yun Fan

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