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

Regan, Joseph L., Sourisseau, Tony, Soady, Kelly, Kendrick, Howard, McCarthy, Afshan, Tang, Chan, Brennan, Keith, Linardopoulos, Spiros, White, Donald E. and Smalley, Matthew John 2013. Aurora A kinase regulates mammary epithelial cell fate by determining mitotic spindle orientation in a Notch-dependent manner. Cell Reports 4 (1) , pp. 110-123. 10.1016/j.celrep.2013.05.044

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
European Cancer Stem Cell Research Institute (ECSCRI)
Subjects: Q Science > QH Natural history > QH301 Biology
Publisher: Cell Press
ISSN: 2211-1247
Date of First Compliant Deposit: 30 March 2016
Last Modified: 24 Apr 2019 12:21
URI: http://orca-mwe.cf.ac.uk/id/eprint/48714

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