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

Hypoxia-inducible factor 1 alpha (HIF-1 alpha) 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-1 alpha and TAZ has reciprocal effects: HIF-1 alpha stimulates transactivation mediated by TAZ and TAZ stimulates transactivation mediated by HIF-1 alpha. 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-1 alpha expression impairs TAZ-mediated transactivation of the CTGF promoter. Taken together, these results complement our previous findings and establish bidirectional crosstalk between HIF-1 alpha and TAZ that increases their transcriptional activities in hypoxic cells.