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

Oncotarget. 2016 Mar 22;7(12):13706-16. doi: 10.18632/oncotarget.7333.

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.

Keywords: Heregulin β1 (HRG1); Hippo pathway; MRTF/SRF; TAZ; breast cancer.

MeSH terms

  • Acyltransferases
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Hemeproteins / genetics
  • Hemeproteins / metabolism*
  • Humans
  • Serum Response Factor / genetics
  • Serum Response Factor / metabolism*
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Hemeproteins
  • MRTFA protein, human
  • SLC48A1 protein, human
  • SRF protein, human
  • Serum Response Factor
  • Trans-Activators
  • Transcription Factors
  • Acyltransferases
  • TAFAZZIN protein, human