Document Detail

Non-cell autonomous control of apoptosis by ligand-independent Hedgehog signaling in Drosophila.
MedLine Citation:
PMID:  23018595     Owner:  NLM     Status:  MEDLINE    
Hedgehog (Hh) signaling is important for development and homeostasis in vertebrates and invertebrates. Ligand-independent, deregulated Hh signaling caused by loss of negative regulators such as Patched causes excessive cell proliferation, leading to overgrowth in Drosophila and tumors in humans, including basal-cell carcinoma and medulloblastoma. We show that in Drosophila deregulated Hh signaling also promotes cell survival by increasing the resistance to apoptosis. Surprisingly, cells with deregulated Hh activity do not protect themselves from apoptosis; instead, they promote cell survival of neighboring wild-type cells. This non-cell autonomous effect is mediated by Hh-induced Notch signaling, which elevates the protein levels of Drosophila inhibitor of apoptosis protein-1 (Diap-1), conferring resistance to apoptosis. In summary, we demonstrate that deregulated Hh signaling not only promotes proliferation but also cell survival of neighboring cells. This non-cell autonomous control of apoptosis highlights an underappreciated function of deregulated Hh signaling, which may help to generate a supportive micro-environment for tumor development.
A E Christiansen; T Ding; Y Fan; H K Graves; H-M Herz; J L Lindblad; A Bergmann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-28
Journal Detail:
Title:  Cell death and differentiation     Volume:  20     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-15     Completed Date:  2013-06-21     Revised Date:  2014-02-07    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  302-11     Citation Subset:  IM    
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MeSH Terms
Drosophila Proteins / genetics,  metabolism*
Hedgehog Proteins / metabolism*
Inhibitor of Apoptosis Proteins / genetics,  metabolism
Kinesin / metabolism
Neuropeptides / genetics,  metabolism
Receptors, Notch / metabolism
Signal Transduction
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/Drosophila Proteins; 0/Hedgehog Proteins; 0/Inhibitor of Apoptosis Proteins; 0/Ligands; 0/Neuropeptides; 0/Receptors, Notch; 0/cos protein, Drosophila; 0/notch protein, Drosophila; 0/thread protein, Drosophila; 0/wrinkled protein, Drosophila; EC 3.6.1.-/Kinesin

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