Abstract
In Drosophila imaginal epithelia, cells mutant for the endocytic neoplastic tumor suppressor gene vps25 stimulate nearby untransformed cells to express Drosophila Inhibitor-of-Apoptosis-Protein-1 (DIAP-1), conferring resistance to apoptosis non-cell autonomously. Here, we show that the non-cell autonomous induction of DIAP-1 is mediated by Yorkie, the conserved downstream effector of Hippo signaling. The non-cell autonomous induction of Yorkie is due to Notch signaling from vps25 mutant cells. Moreover, activated Notch in normal cells is sufficient to induce non-cell autonomous Yorkie activity in wing imaginal discs. Our data identify a novel mechanism by which Notch promotes cell survival non-cell autonomously and by which neoplastic tumor cells generate a supportive microenvironment for tumor growth.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Drosophila
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Endosomal Sorting Complexes Required for Transport / genetics
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Immunohistochemistry
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Inhibitor of Apoptosis Proteins / genetics
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Inhibitor of Apoptosis Proteins / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Receptors, Notch / genetics
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Receptors, Notch / metabolism*
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Signal Transduction / genetics
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Signal Transduction / physiology
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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YAP-Signaling Proteins
Substances
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DIAP1 protein, Drosophila
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Drosophila Proteins
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Endosomal Sorting Complexes Required for Transport
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Inhibitor of Apoptosis Proteins
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N protein, Drosophila
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Nuclear Proteins
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Receptors, Notch
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Trans-Activators
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Vps25 protein, Drosophila
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YAP-Signaling Proteins
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Yki protein, Drosophila