CRB3 regulates contact inhibition by activating the Hippo pathway in mammary epithelial cells

Cell Death Dis. 2017 Jan 12;8(1):e2546. doi: 10.1038/cddis.2016.478.

Abstract

The loss of contact inhibition is a hallmark of cancer cells. The Hippo pathway has recently been shown to be an important regulator of contact inhibition, and the cell apical polarity determinant protein CRB3 has been suggested to be involved in Hippo signalling. However, whether CRB3 regulates contact inhibition in mammary cells remains unclear, and the underlying mechanisms have not been elucidated. As shown in the present study, CRB3 decreases cell proliferation, promotes apoptosis, and enhances the formation of tight and adherens junctions. Furthermore, we report for the first time that CRB3 acts as an upstream regulator of the Hippo pathway to regulate contact inhibition by recruiting other Hippo molecules, such as Kibra and/or FRMD6, in mammary epithelial cells. In addition, CRB3 inhibits tumour growth in vivo. Collectively, the present study increases our understanding of the Hippo pathway and provides an important theoretical basis for exploring new avenues for breast cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Polarity / genetics
  • Cell Proliferation / genetics
  • Contact Inhibition / genetics*
  • Cytoskeletal Proteins / genetics*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Mammary Glands, Human / metabolism*
  • Membrane Glycoproteins / genetics*
  • Membrane Proteins / genetics*
  • Mice
  • Phosphoproteins / genetics*
  • Protein-Serine-Threonine Kinases / genetics

Substances

  • CRB3 protein, human
  • Cytoskeletal Proteins
  • FRMD6 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Phosphoproteins
  • WWC1 protein, human
  • Hippo protein, human
  • Protein-Serine-Threonine Kinases