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

33 Citations (Scopus)

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
StatePublished - Jan 1 2015

Fingerprint

Breast Neoplasms
Transcriptional Activation
Hypoxia
Proteins
Neoplasm Metastasis
Mortality
Genes

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Xiang, L., Gilkes, D. M., Hu, H., Luo, W., Bullen, J. W., Liang, H., & Semenza, G. L. (2015). HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells. Oncotarget, 6(14), 11768-11778.

HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells. / Xiang, Lisha; Gilkes, Daniele M.; Hu, Hongxia; Luo, Weibo; Bullen, John W.; Liang, Houjie; Semenza, Gregg L.

In: Oncotarget, Vol. 6, No. 14, 01.01.2015, p. 11768-11778.

Research output: Contribution to journalArticle

Xiang, L, Gilkes, DM, Hu, H, Luo, W, Bullen, JW, Liang, H & Semenza, GL 2015, 'HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells', Oncotarget, vol. 6, no. 14, pp. 11768-11778.
Xiang L, Gilkes DM, Hu H, Luo W, Bullen JW, Liang H et al. HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells. Oncotarget. 2015 Jan 1;6(14):11768-11778.
Xiang, Lisha ; Gilkes, Daniele M. ; Hu, Hongxia ; Luo, Weibo ; Bullen, John W. ; Liang, Houjie ; Semenza, Gregg L. / HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells. In: Oncotarget. 2015 ; Vol. 6, No. 14. pp. 11768-11778.
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