The Wnt-β-catenin signaling regulated MRTF-A transcription to activate migration-related genes in human breast cancer cells
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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
Hongpeng He, email: [email protected]
Tong-Cun Zhang, email: [email protected]
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
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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