In Drosophila, epithelial tissues that are homozygous mutant for any of the neoplastic tumor suppressor genes (nTSGs), including scrib, Dlg, and Lgl, lose epithelial structures and form amorphous tumors. However, when these nTSG-mutant cells are confronted with normal cells, cell competition leads to the elimination of nTSG-mutant cells. Modulating multiple oncogenic signaling pathways, including the activation of Yki, EGFR signaling, and Notch signaling by overexpressing Yki^S168A, Ras^V12,and NICD, respectively, rescues scrib mutant clonal cells from cell competition-induced elimination and promotes tumor growth. It is unclear how these signaling pathways change scrib mutant cell fate and whether they convert the scrib mutant loser cell fate into winner cell fate through the same or dif...[ Read more ]

In Drosophila, epithelial tissues that are homozygous mutant for any of the neoplastic tumor suppressor genes (nTSGs), including scrib, Dlg, and Lgl, lose epithelial structures and form amorphous tumors. However, when these nTSG-mutant cells are confronted with normal cells, cell competition leads to the elimination of nTSG-mutant cells. Modulating multiple oncogenic signaling pathways, including the activation of Yki, EGFR signaling, and Notch signaling by overexpressing Yki^S168A, Ras^V12,and NICD, respectively, rescues scrib mutant clonal cells from cell competition-induced elimination and promotes tumor growth. It is unclear how these signaling pathways change scrib mutant cell fate and whether they convert the scrib mutant loser cell fate into winner cell fate through the same or different mechanisms. To answer this question and understand the source of tumor cell plasticity, we performed single cell transcriptomic analysis for winner and loser cells during cell competition in various genetic backgrounds. We found that these oncogenic pathways do not affect the cell proliferation ability ofthe scrib mutant cells and can partially reduce cell death in the scrib mutant cells without affecting JNK activity. Oncogenic Ras, NICD, and Yki signals in scrib mutant clones can upregulate upd2 autonomously and activate STAT and mTOR signaling non-autonomously in wild-type cells neighboring the scrib mutant clones. Knockdown of upd2 can restrict tumor growth.