?Np63 regulates the expression of hyaluronic acid-related genes in breast cancer cells

Triple negative breast cancers (TNBC) represent the most aggressive and clinically relevant breast carcinomas. On the basis of specific molecular signature, the majority of TNBC can be classified as basal-like breast carcinoma. Here, we report data showing that in basal-like breast carcinoma cells ?Np63 is capable of sustaining the production of the hyaluronic acid (HA), one of the major component of the extracellular matrix (ECM). At molecular level, we found that ?Np63 regulates the expression of HA-related genes, such as the HA synthase HAS3, the hyaluronidase HYAL-1 and CD44, the major HA cell membrane receptor. By controlling this pathway, ?Np63 contributes to maintain the self-renewal of breast cancer stem cells. Importantly, high HAS3 expression is a negative prognostic factor of TNBC patients. Our data suggest that in basal-type breast carcinoma ?Np63 might favor a HA-rich microenviroment, which can sustain tumor proliferation and stemness.