Identification of RUNX3 as a component of the MST/Hpo signaling pathway

Boram Min, Min Kyu Kim, Joo Won Zhang, Jiyeon Kim, Kwang Chul Chung, Byung Chul Oh, Gary S. Stein, Yong Hee Lee, Andre J van Wijnen, Suk Chul Bae

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)839-849
Number of pages11
JournalJournal of Cellular Physiology
Volume227
Issue number2
DOIs
StatePublished - Jan 2012
Externally publishedYes

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Cell death
Tumors
Cell Death
Neoplasms
Deregulation
Urinary Bladder Neoplasms
Colonic Neoplasms
Cell proliferation
Lung Neoplasms
Small Interfering RNA
Diptera
Stomach Neoplasms
Cell Proliferation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Min, B., Kim, M. K., Zhang, J. W., Kim, J., Chung, K. C., Oh, B. C., ... Bae, S. C. (2012). Identification of RUNX3 as a component of the MST/Hpo signaling pathway. Journal of Cellular Physiology, 227(2), 839-849. https://doi.org/10.1002/jcp.22887

Identification of RUNX3 as a component of the MST/Hpo signaling pathway. / Min, Boram; Kim, Min Kyu; Zhang, Joo Won; Kim, Jiyeon; Chung, Kwang Chul; Oh, Byung Chul; Stein, Gary S.; Lee, Yong Hee; van Wijnen, Andre J; Bae, Suk Chul.

In: Journal of Cellular Physiology, Vol. 227, No. 2, 01.2012, p. 839-849.

Research output: Contribution to journalArticle

Min, B, Kim, MK, Zhang, JW, Kim, J, Chung, KC, Oh, BC, Stein, GS, Lee, YH, van Wijnen, AJ & Bae, SC 2012, 'Identification of RUNX3 as a component of the MST/Hpo signaling pathway', Journal of Cellular Physiology, vol. 227, no. 2, pp. 839-849. https://doi.org/10.1002/jcp.22887
Min, Boram ; Kim, Min Kyu ; Zhang, Joo Won ; Kim, Jiyeon ; Chung, Kwang Chul ; Oh, Byung Chul ; Stein, Gary S. ; Lee, Yong Hee ; van Wijnen, Andre J ; Bae, Suk Chul. / Identification of RUNX3 as a component of the MST/Hpo signaling pathway. In: Journal of Cellular Physiology. 2012 ; Vol. 227, No. 2. pp. 839-849.
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