Cell Competition Drives the Formation of Metastatic Tumors in a Drosophila Model of Epithelial Tumor Formation

• Published in: Current biology 2016-02, Vol.26 (4), p.419-427
• Main Authors: Eichenlaub, Teresa, Cohen, Stephen M., Herranz, Héctor
• Format: Article
• Language: English
• Subjects: Animals; Carcinogenesis; Cell Proliferation; Cell Transformation, Neoplastic; Disease Models, Animal; Drosophila melanogaster - growth & development; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Humans; MicroRNAs - genetics; MicroRNAs - metabolism; Neoplasms, Glandular and Epithelial - etiology; Neoplasms, Glandular and Epithelial - physiopathology; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Receptors, Invertebrate Peptide - genetics; Receptors, Invertebrate Peptide - metabolism
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2015.12.042

Cell competition is a homeostatic process in which proliferating cells compete for survival. Elimination of otherwise normal healthy cells through competition is important during development and has recently been shown to contribute to maintaining tissue health during organismal aging. The mechanisms that allow for ongoing cell competition during adult life could, in principle, contribute to tumorigenesis. However, direct evidence supporting this hypothesis has been lacking. Here, we provide evidence that cell competition drives tumor formation in a Drosophila model of epithelial cancer. Cells expressing EGFR together with the conserved microRNA miR-8 acquire the properties of supercompetitors. Neoplastic transformation and metastasis depend on the ability of these cells to induce apoptosis and engulf nearby cells. miR-8 expression causes genome instability by downregulating expression of the Septin family protein Peanut. Cytokinesis failure due to downregulation of Peanut is required for tumorigenesis. This study provides evidence that the cellular mechanisms that drive cell competition during normal tissue growth can be co-opted to drive tumor formation and metastasis. Analogous mechanisms for cytokinesis failure may lead to polyploid intermediates in tumorigenesis in mammalian cancer models. •Cytokinesis failure drives tumor formation in the context of EGFR overexpression•Cytokinesis failure leads to formation of giant polyploid tumor cells•Giant cells drive tumor formation by inducing apoptosis of nearby cells•Apoptosis and cell engulfment are required for formation of the giant cells Eichenlaub et al. present a genetic model for cell competition in tumor formation. In the context of EGFR expression, cytokinesis failure initiates formation of giant polyploid cells. These cells drive tumor formation by inducing apoptosis of nearby cells and engulfing the “losers.” Tumor formation depends on inducing apoptosis in nearby cells.