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

// Hongpeng He 1 , Fu Du 1 , Yongping He 1 , Zhaoqiang Wei 1 , Chao Meng 1 , Yuexin Xu 2 , Hao Zhou 1 , Nan Wang 1 , Xue-Gang Luo 1 , Wenjian Ma 1 and Tong-Cun Zhang 1, 3 1 Key Laboratory of Industrial Microbiology, Ministry of Education and Tianjin City, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, P. R. China 2 Department of Pathology, Mentougou Hospital in Beijing, 102300, Beijing, P.R. China 3 College 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.