HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells

Lisha Xiang, Daniele M. Gilkes, Hongxia Hu, Weibo Luo, John W. Bullen, Houjie Liang, Gregg L. Semenza

Research output: Contribution to journalArticle

Abstract

Hypoxia-inducible factor 1a (HIF-1α) expression is a hallmark of intratumoral hypoxia that is associated with breast cancer metastasis and patient mortality. Previously, we demonstrated that HIF-1 stimulates the expression and activity of TAZ, which is a transcriptional effector of the Hippo signaling pathway, by increasing TAZ synthesis and nuclear localization. Here, we report that direct protein-protein interaction between HIF-1α and TAZ has reciprocal effects: HIF-1α stimulates transactivation mediated by TAZ and TAZ stimulates transactivation mediated by HIF-1α. Inhibition of TAZ expression impairs the hypoxic induction of HIF-1 target genes, such as PDK1, LDHA, BNIP3 and P4HA2 in response to hypoxia, whereas inhibition of HIF-1α expression impairs TAZ-mediated transactivation of the CTGF promoter. Taken together, these results complement our previous findings and establish bidirectional crosstalk between HIF-1α and TAZ that increases their transcriptional activities in hypoxic cells.

Original languageEnglish (US)
Pages (from-to)11768-11778
Number of pages11
JournalOncotarget
Volume6
Issue number14
DOIs
StatePublished - Jan 1 2015

Keywords

  • Breast cancer progression
  • Hypoxia-inducible factor 1
  • MCF-7 cells
  • MDA-MB-231 cells

ASJC Scopus subject areas

  • Oncology

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