In Drosophila, epithelial tissues with homozygous mutant for any of the neoplastic tumor suppressor genes (nTSGs), including Scrib, Dlg and Lgl, will lose epithelial structures and form amorphous tumors. However, when these nTSGs mutant cells are confronted with normal cells, a cell competition process lead to elimination of nTSGs mutant cells. The JNK, Hippo, Notch and EGFR signaling pathways have been reported to play a role in regulating Scrib mutation-induced cell competition. We found that modulation of these signaling pathways will rescue Scrib-depleted cells from cell competition-induced elimination and promote tumor overgrowth, include blockage of JNK signaling through overexpressing Bsk^DN, activation of Yki activity through overexpressing Yki or YkiS168A, activation of...[ Read more ]

In Drosophila, epithelial tissues with homozygous mutant for any of the neoplastic tumor suppressor genes (nTSGs), including Scrib, Dlg and Lgl, will lose epithelial structures and form amorphous tumors. However, when these nTSGs mutant cells are confronted with normal cells, a cell competition process lead to elimination of nTSGs mutant cells. The JNK, Hippo, Notch and EGFR signaling pathways have been reported to play a role in regulating Scrib mutation-induced cell competition. We found that modulation of these signaling pathways will rescue Scrib-depleted cells from cell competition-induced elimination and promote tumor overgrowth, include blockage of JNK signaling through overexpressing Bsk^DN, activation of Yki activity through overexpressing Yki or YkiS168A, activation of EGFR signaling activity through overexpressing Ras^V12 and activation of Notch signaling through overexpressing NICD. To dissect whether and how these signaling pathways affect the growth outcome of Scrib-depleted cell clones, we performed transcriptome analysis of these tumors with signaling pathway modulations. These data will allow us to systematically map the Ras, Notch, Hippo and JNK signaling network in the drosophila nTSG tumor growth model and identify key codes in the network determining the growth outcome of nTSG mutant cells.