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 language | English (US) |
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Pages (from-to) | 11768-11778 |
Number of pages | 11 |
Journal | Oncotarget |
Volume | 6 |
Issue number | 14 |
DOIs | |
State | Published - 2015 |
Keywords
- Breast cancer progression
- Hypoxia-inducible factor 1
- MCF-7 cells
- MDA-MB-231 cells
ASJC Scopus subject areas
- Oncology