Priority Research Papers:
HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells
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Lisha Xiang1,2,3, Daniele M. Gilkes2,3, Hongxia Hu2,3, Weibo Luo2,3, John W. Bullen2,3, Houjie Liang1 and Gregg L. Semenza2,3,4
1 Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China
2 Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
3 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
4 Departments of Pediatrics, Medicine, Oncology, Radiation Oncology, and Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Gregg L. Semenza, email:
Keywords: breast cancer progression, hypoxia-inducible factor 1, MDA-MB-231 cells, MCF-7 cells
Received: May 05, 2015 Accepted: May 05, 2015 Published: May 19, 2015
Hypoxia-inducible factor 1α (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.
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