Aurora A kinase regulates mammary epithelial cell fate by determining mitotic spindle orientation in a Notch-dependent manner

Cell Rep. 2013 Jul 11;4(1):110-23. doi: 10.1016/j.celrep.2013.05.044. Epub 2013 Jun 27.


Cell fate determination in the progeny of mammary epithelial stem/progenitor cells remains poorly understood. Here, we have examined the role of the mitotic kinase Aurora A (AURKA) in regulating the balance between basal and luminal mammary lineages. We find that AURKA is highly expressed in basal stem cells and, to a lesser extent, in luminal progenitors. Wild-type AURKA expression promoted luminal cell fate, but expression of an S155R mutant reduced proliferation, promoted basal fate, and inhibited serial transplantation. The mechanism involved regulation of mitotic spindle orientation by AURKA and the positioning of daughter cells after division. Remarkably, this was NOTCH dependent, as NOTCH inhibitor blocked the effect of wild-type AURKA expression on spindle orientation and instead mimicked the effect of the S155R mutant. These findings directly link AURKA, NOTCH signaling, and mitotic spindle orientation and suggest a mechanism for regulating the balance between luminal and basal lineages in the mammary gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology
  • Adult Stem Cells / metabolism
  • Animals
  • Aurora Kinase A / genetics
  • Aurora Kinase A / metabolism*
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation
  • Cell Lineage*
  • Cell Proliferation
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Female
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / metabolism*
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Mutation
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Receptor, Notch1 / metabolism*
  • Spindle Apparatus / metabolism*


  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Notch1 protein, mouse
  • Nuclear Proteins
  • Receptor, Notch1
  • TPX2 protein, mouse
  • Aurka protein, mouse
  • Aurora Kinase A