Notch signaling activates Yorkie non-cell autonomously in Drosophila.
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.
Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Hillary K
HK
Graves
Sarah E
SE
Woodfield
Chih-Chao
CC
Yang
Georg
G
Halder
Andreas
A
Bergmann
D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
C111891:DIAP1 protein, Drosophila; D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D051034:Inhibitor of Apoptosis Proteins; C497759:N protein, Drosophila; D009687:Nuclear Proteins; D051880:Receptors, Notch; D015534:Trans-Activators; C511665:Vps25 protein, Drosophila; D000091102:YAP-Signaling Proteins; C503814:Yki protein, Drosophila