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Biochem Biophys Res Commun. 2013 Jul 5;436(3):436-42. doi: 10.1016/j.bbrc.2013.05.122. Epub 2013 Jun 6.

Identification of HDAC4 as a target of γ-catenin that regulates the oncogenic K-Ras-mediated malignant phenotype of Rat2 cells.

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  • 1Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.


The mechanisms by which activated Ras accelerates malignant transformation of normal cells are not fully understood. Here, we characterized the role and molecular mechanism of γ-catenin in regulating the malignant phenotype of Rat2 cells induced by codon 12-mutant K-Ras (K-Ras12V). Suppression of γ-catenin signaling by K-Ras12V was an early event and played a crucial role in promoting the acquisition of a highly metastatic phenotype of Rat2 cells. Notably, the gene encoding histone deacetylase 4 (HDAC4) was identified as a target of γ-catenin during this process. The transcription factor, lymphoid enhancer-binding factor-1 (Lef1), was involved in the modulation of HDAC4 transcription, and disruption of this pathway was a key event in promoting the invasion and migration of K-Ras12V-transduced Rat2 cells. Thus, our findings extend the range of targets for the development of new drugs for the therapy of oncogenic K-Ras-driven cancer.

Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.


HDAC4; Lef1; Oncogenic K-Ras; Rat2 fibroblast cells; γ-Catenin

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