A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis

Genes Dev. 2014 Mar 1;28(5):432-7. doi: 10.1101/gad.233676.113.


Despite recent progress, the physiological role of Hippo signaling in mammary gland development and tumorigenesis remains poorly understood. Here we show that the Hippo pathway is functionally dispensable in virgin mammary glands but specifically required during pregnancy. In contrast to many other tissues, hyperactivation of YAP in mammary epithelia does not induce hyperplasia but leads to defects in terminal differentiation. Interestingly, loss of YAP causes no obvious defects in virgin mammary glands but potently suppresses oncogene-induced mammary tumors. The selective requirement for YAP in oncogenic growth highlights the potential of YAP inhibitors as molecular targeted therapies against breast cancers.

Keywords: Hippo signaling; YAP; differentiation; mammary gland; proliferation; tumorigenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Carcinogenesis / pathology*
  • Cell Differentiation*
  • Female
  • Hippo Signaling Pathway
  • Mammary Glands, Animal / cytology*
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / pathology*
  • Mammary Neoplasms, Animal / pathology*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Oncogenes / genetics
  • Pregnancy
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction*
  • Time


  • Protein Serine-Threonine Kinases