TY - JOUR
T1 - Loss of polarity alters proliferation and differentiation in low-grade endometrial cancers by disrupting Notch signaling
AU - Williams, Erin
AU - Villar-Prados, Alejandro
AU - Bowser, Jessica
AU - Broaddus, Russell
AU - Gladden, Andrew B.
N1 - Publisher Copyright:
© 2017 Williams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/12
Y1 - 2017/12
N2 - Cell adhesion and apicobasal polarity together maintain epithelial tissue organization and homeostasis. Loss of adhesion has been described as a prerequisite for the epithelial to mesenchymal transition. However, what role misregulation of apicobasal polarity promotes tumor initiation and/or early progression remains unclear. We find that human low-grade endometrial cancers are associated with disrupted localization of the apical polarity protein Par3 and Ezrin while, the adhesion molecule E-cadherin remains unchanged, accompanied by decreased Notch signaling, and altered Notch receptor localization. Depletion of Par3 or Ezrin, in a cell-based model, results in loss of epithelial architecture, differentiation, increased proliferation, migration and decreased Notch signaling. Re-expression of Par3 in endometrial cancer cell lines with disrupted Par3 protein levels blocks proliferation and reduces migration in a Notch dependent manner. These data uncover a function for apicobasal polarity independent of cell adhesion in regulating Notch-mediated differentiation signals in endometrial epithelial cells.
AB - Cell adhesion and apicobasal polarity together maintain epithelial tissue organization and homeostasis. Loss of adhesion has been described as a prerequisite for the epithelial to mesenchymal transition. However, what role misregulation of apicobasal polarity promotes tumor initiation and/or early progression remains unclear. We find that human low-grade endometrial cancers are associated with disrupted localization of the apical polarity protein Par3 and Ezrin while, the adhesion molecule E-cadherin remains unchanged, accompanied by decreased Notch signaling, and altered Notch receptor localization. Depletion of Par3 or Ezrin, in a cell-based model, results in loss of epithelial architecture, differentiation, increased proliferation, migration and decreased Notch signaling. Re-expression of Par3 in endometrial cancer cell lines with disrupted Par3 protein levels blocks proliferation and reduces migration in a Notch dependent manner. These data uncover a function for apicobasal polarity independent of cell adhesion in regulating Notch-mediated differentiation signals in endometrial epithelial cells.
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U2 - 10.1371/journal.pone.0189081
DO - 10.1371/journal.pone.0189081
M3 - Article
C2 - 29206870
AN - SCOPUS:85036606825
SN - 1932-6203
VL - 12
JO - PloS one
JF - PloS one
IS - 12
M1 - e0189081
ER -