title: Identification of RUNX3 as a component of the MST/Hpo signaling pathway.
abstract: Recent 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.
authors.affiliation: Department of Biochemistry, School of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Min
authors.forename: Min-Kyu
authors.initials: MK
authors.lastname: Kim
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Zhang
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Kim
authors.forename: Kwang-Chul
authors.initials: KC
authors.lastname: Chung
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Oh
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Lee
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.forename: Suk-Chul
authors.initials: SC
authors.lastname: Bae
mesh_terms: D000818:Animals; D005075:Biological Evolution; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D000099317:Hippo Kinases
chemical_list: D018797:Cell Cycle Proteins; D050677:Core Binding Factor Alpha 3 Subunit; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D017346:Protein Serine-Threonine Kinases; C493729:Runx3 protein, human; C415864:SAV1 protein, human; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases; C093290:MAP3K10 protein, human