The Wnt-β-catenin signaling regulated MRTF-A transcription to activate migration-related genes in human breast cancer cells
- Oncotarget. 2018 Jan 4;9(20):15239-15251. doi: 10.18632/oncotarget.23961.
- 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.
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.