Figure 8. Effect of HIF and TAZ activity on tumorigenicity and patient survival.
(A) To analyze the tumor-initiating capacity of the NTC, sh1α, sh2α, and shT1 subclones, 1000 cells were injected into the mammary fat pad of immunodeficient female mice. The table reports the number of mice developing palpable tumors after 71 d. The Chi-square test was performed to determine statistical significance versus NTC; n.s., not significant. (B) Kaplan–Meier analysis of disease-specific survival for 1,098 breast cancer patients stratified by TAZ and HIF signatures in the primary tumor. High, High (red): patients with both TAZ and HIF signatures greater than the median (N = 356). Low, High (green): patients with TAZ or HIF signature greater than the median and the other signature less than the median (N = 382). Low, Low (blue): patients with both signatures less than the median (N = 360). The Wilcoxon rank sum test was used to compare survival curves (**P < 0.01, ***P < 0.001). (C) HIF-1 activates transcription of the WWTR1 and SIAH1 genes to stimulate TAZ expression and nuclear localization, respectively, and induce the breast cancer stem cell phenotype in response to hypoxia.