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Identification of RUNX3 as a component of the MST/Hpo signaling pathway
Author(s) -
Min Boram,
Kim MinKyu,
Zhang JooWon,
Kim Jiyeon,
Chung KwangChul,
Oh ByungChul,
Stein Gary S.,
Lee YongHee,
van Wijnen Andre J.,
Bae SukChul
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22887
Subject(s) - component (thermodynamics) , identification (biology) , signal transduction , computational biology , microbiology and biotechnology , chemistry , biology , botany , physics , thermodynamics
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. J. Cell. Physiol. 227: 839–849, 2012. © 2011 Wiley Periodicals, Inc.