Chen-Ying Liu1,2, Siew Wee Chan1, Fusheng Guo1, Aleksandra Toloczko1, Long Cui2,3, Wanjin Hong1,3
1 Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 61, Biopolis Drive, Proteos, Singapore 138673, Singapore;
2 Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
3 Correspondence: Wanjin Hong, email: firstname.lastname@example.org;
Long Cui, email: email@example.com
Published in Oncotarget on 11 February 2016. (doi: 10.18632/oncotarget.7333.)
Dysregulation of Hippo pathway results in activation of transcriptional co-activators YAP/TAZ, leading to tumorigenesis and tumor progression, which occurs in multiple cancers including breast cancer. Previously, we showed that upregulation of TAZ in breast cancer which plays a vital role in cell migration, invasion and tumorigenesis. Here, we show that upregulation of TAZ in breast cancers could also be due to the dysregulation of TAZ transcription. Heregulin b1 (HRG1) promotes TAZ mRNA expression level in breast cancer cells. TAZ is a direct target of MRTF/SRF transcriptional factors which are activated by HRG1 in breast cancer cells. Both MRTF/SRF and TAZ are the important downstream effectors mediating the biological function of HRG1. The mRNA expression level of TAZ is correlated with nuclear localization of MRTF in breast cancer cells and the expression level of MRTF/SRF direct target genes in breast cancers, which indicate the association between MRTF/SRF activity and TAZ expression in breast cancers. Our results provide new insights into the transcriptional regulation of TAZ and dysregulation mechanism of TAZ in breast cancers, which could be a new therapeutic strategy for breast cancer treatment.
Figure legend: Correlation between TAZ and MRTF/SRF pathway in the TCGA breast cancer database. (A) TAZ expression level is correlated with the expression level of MRTF/SRF target genes in breast cancer. Co-expression data between TAZ and FLNA, SRF, MYH9, and VCL, respectively, in the breast cancer TCGA RNA-seq data were extracted from the cbioportal database. The value of Pearson's correlation coefficient and Spearman’s correlation coefficient were generated by the cbioportal database to measure the correlation of gene co-expression. (B) The expression levels of TAZ and MRTF/SRF target genes in the TCGA datasets from UCSC Cancer genomics browser were shown.
For more information on Wanjin HONG's lab, please click here.