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

Lisha Xiang, Daniele 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
StatePublished - 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., 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; Hu, Hongxia; Luo, Weibo; Bullen, John W.; Liang, Houjie; Semenza, Gregg L.

In: Oncotarget, Vol. 6, No. 14, 2015, p. 11768-11778.

Research output: Contribution to journalArticle

Xiang, L, Gilkes, D, 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 D, 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;6(14):11768-11778.
Xiang, Lisha ; Gilkes, Daniele ; 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.
@article{53b49824059a4578a183950a0492c687,
title = "HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells",
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.",
keywords = "Breast cancer progression, Hypoxia-inducible factor 1, MCF-7 cells, MDA-MB-231 cells",
author = "Lisha Xiang and Daniele Gilkes and Hongxia Hu and Weibo Luo and Bullen, {John W.} and Houjie Liang and Semenza, {Gregg L}",
year = "2015",
language = "English (US)",
volume = "6",
pages = "11768--11778",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "14",

}

TY - JOUR

T1 - HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells

AU - Xiang, Lisha

AU - Gilkes, Daniele

AU - Hu, Hongxia

AU - Luo, Weibo

AU - Bullen, John W.

AU - Liang, Houjie

AU - Semenza, Gregg L

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Breast cancer progression

KW - Hypoxia-inducible factor 1

KW - MCF-7 cells

KW - MDA-MB-231 cells

UR - http://www.scopus.com/inward/record.url?scp=84931298020&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84931298020&partnerID=8YFLogxK

M3 - Article

C2 - 26059435

AN - SCOPUS:84931298020

VL - 6

SP - 11768

EP - 11778

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 14

ER -