Mechanism of tumor-suppressive cell competition in flies.

Oncogenic mutations often trigger antitumor 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 the 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.