Oncotarget

Research Papers:

The Wnt-β-catenin signaling regulated MRTF-A transcription to activate migration-related genes in human breast cancer cells

Hongpeng He _, Fu Du, Yongping He, Zhaoqiang Wei, Chao Meng, Yuexin Xu, Hao Zhou, Nan Wang, Xue-Gang Luo, Wenjian Ma and Tong-Cun Zhang

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Oncotarget. 2018; 9:15239-15251. https://doi.org/10.18632/oncotarget.23961

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Abstract

Hongpeng He1, Fu Du1, Yongping He1, Zhaoqiang Wei1, Chao Meng1, Yuexin Xu2, Hao Zhou1, Nan Wang1, Xue-Gang Luo1, Wenjian Ma1 and Tong-Cun Zhang1,3

1Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, P. R. China

2Department of Pathology, Mentougou Hospital in Beijing, 102300, Beijing, P.R. China

3College of Life Sciences, Wuhan University of Science and Technology, 430081, Wuhan, P. R. China

Correspondence to:

Hongpeng He, email: hehongpeng@tust.edu.cn

Tong-Cun Zhang, email: tony@tust.edu.cn

Keywords: breast cancer; metastasis; MRTF-A; Rho-actin; Wnt-β-catenin

Received: July 31, 2017     Accepted: November 16, 2017     Epub: January 04, 2018     Published: March 16, 2018

ABSTRACT

MRTF-A is a transcriptional co-activator being critical for multiple processes including tissue fibrosis and cancer metastasis. The Rho-actin signaling stimulates the nuclear translocation and transcriptional activity of MRTF-A with little effect on the expression of MRTF-A gene. High expression of MRTF-A was observed in pancreatic cancer tissues and in TGF-β treated breast cancer cells. However, the mechanism for the upregulation of MRTF-A gene remains unclear. In this study, we showed that the transcription of MRTF-A was regulated by the Wnt-β-catenin signaling in breast cancer cells. LiCl treatment, Wnt3a treatment or β-catenin overexpression enhanced the transcription of MRTF-A gene. In agreement, depletion of β-catenin with siRNA diminished MRTF-A transcription. With ChIP assays, β-catenin was identified to interact with the MRTF-A promoter whereby it increased histone H4 acetylation and RNA polymerase II association. Further, results of RT-qPCR and Western-blotting supported that the transcriptional co-activator activity of MRTF-A was controlled by both the Rho-actin and the Wnt-β-catenin signaling pathways. MRTF-A was required for cell migration stimulated by the Wnt-β-catenin signaling. Taken together, our results suggest that MRTF-A integrates the Rho-actin and the Wnt-β-catenin signaling to regulate migration-related genes and consequently increases the mobility of breast cancer cells.


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