Loss of periostin activates an AR response. Through an unknown mechanism, the presence of Postn in the microenvironment stimulates or maintains Notch processing and NICD activity (1). Loss of periostin (2) results in NICD downregulation and AR upregulation by an undefined mechanism (dotted lines). This is accompanied by Hey1 downregulation and the activation of AR target genes without any effect on development. Activation of the AR pathway or Notch signaling is sufficient to drive normal mammary tumor progression. However, in a Postn-deficient environment tumor growth at heterotopic sites is impaired (3).