MRTF/SRF dependent transcriptional regulation of TAZ in breast cancer cells

// Chen-Ying Liu 1, 2 , Siew Wee Chan 1 , Fusheng Guo 1 , Aleksandra Toloczko 1 , Long Cui 2 , Wanjin Hong 1 1 Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Proteos, Singapore 138673, Singapore 2 Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China Correspondence to: Wanjin Hong, e-mail: mcbhwj@imcb.a-star.edu.sg Long Cui, e-mail: longcuidr@126.com Keywords: Hippo pathway, TAZ, MRTF/SRF, Heregulin β1 (HRG1), breast cancer Received: November 11, 2015      Accepted: January 29, 2016      Published: February 11, 2016 ABSTRACT Dysregulation of Hippo pathway results in activation of transcriptional co-activators YAP/TAZ in breast cancer. Previously, we showed that overexpression of TAZ in breast cancer promotes cell migration, invasion and tumorigenesis. Here, we show that upregulation of TAZ in breast cancers could also be due to dysregulation of TAZ transcription. Heregulin β1 (HRG1) increases TAZ mRNA level in breast cancer cells. TAZ is a direct target of MRTF/SRF transcriptional factors which are activated by HRG1. Both MRTF/SRF and TAZ are the important downstream effectors enhancing cell migration induced by HRG1. TAZ mRNA level is correlated with nuclear localization of MRTF in breast cancer cells and the mRNA level of MRTF/SRF direct target genes in breast cancers, indicating the correlation between MRTF/SRF activity and TAZ expression. Our results provide new insights into the transcriptional regulation of TAZ and dysregulation mechanism of TAZ in breast cancer, which could be a new therapeutic strategy for breast cancer.