Attempting to understand potential mechanisms through which Notch signaling may facilitate tumorigenesis, Tagliabue and colleagues found that Notch1 signaling equipped breast cancer cells with tumor-initiating cell properties due to HER2 gene amplification, and these effects were reduced after blockage of Notch signaling using either γ-secretase inhibition or Notch1-specific silencing (Magnifico et al., 2009). The gene discussed is NOTCH1; the disease is breast cancer.