Identification of RUNX3 as a component of the MST/Hpo signaling pathway
Stein, Gary S.
Van Wijnen, Andre J.
UMass Chan AffiliationsDepartment of Cell Biology
Document TypeJournal Article
Cell Cycle Proteins
Core Binding Factor Alpha 3 Subunit
Gene Expression Regulation
Intracellular Signaling Peptides and Proteins
MAP Kinase Kinase Kinases
Two-Hybrid System Techniques
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AbstractRecent genetic screens of fly mutants and molecular analysis have revealed that the Hippo (Hpo) pathway controls both cell proliferation and cell death. Deregulation of its human counterpart (the MST pathway) has been implicated in human cancers. However, how this pathway is linked with the known tumor suppressor network remains to be established. RUNX3 functions as a tumor suppressor of gastric cancer, lung cancer, bladder cancer, and colon cancer. Here, we show that RUNX3 is a principal and evolutionarily conserved component of the MST pathway. SAV1/WW45 facilitates the close association between MST2 and RUNX3. MST2, in turn, stimulates the SAV1-RUNX3 interaction. In addition, we show that siRNA-mediated RUNX3 knockdown abolishes MST/Hpo-mediated cell death. By establishing that RUNX3 is an endpoint effector of the MST pathway and that RUNX3 is capable of inducing cell death in cooperation with MST and SAV1, we define an evolutionarily conserved novel regulatory mechanism loop for tumor suppression in human cancers.
SourceJ Cell Physiol. 2012 Feb;227(2):839-49. doi: 10.1002/jcp.22887. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/49580
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