E-cadherin Bridges Cell Polarity and Spindle Orientation to Ensure Prostate Epithelial Integrity and Prevent Carcinogenesis in Vivo

Overview

Journal PLoS Genet

Specialty Genetics

Date 2018 Aug 18

PMID 30118484

Citations 29

Authors

Xue Wang

Baijun Dong

Kai Zhang

Zhongzhong Ji

Chaping Cheng

Huifang Zhao

Yaru Sheng

Xiaoxia Li

Liancheng Fan

Wei Xue

Wei-Qiang Gao

Helen He Zhu

Affiliations

Soon will be listed here.

Abstract

Cell polarity and correct mitotic spindle positioning are essential for the maintenance of a proper prostate epithelial architecture, and disruption of the two biological features occurs at early stages in prostate tumorigenesis. However, whether and how these two epithelial attributes are connected in vivo is largely unknown. We herein report that conditional genetic deletion of E-cadherin, a key component of adherens junctions, in a mouse model results in loss of prostate luminal cell polarity and randomization of spindle orientations. Critically, E-cadherin ablation causes prostatic hyperplasia which progresses to invasive adenocarcinoma. Mechanistically, E-cadherin and the spindle positioning determinant LGN interacts with the PDZ domain of cell polarity protein SCRIB and form a ternary protein complex to bridge cell polarity and cell division orientation. These findings provide a novel mechanism by which E-cadherin acts an anchor to maintain prostate epithelial integrity and to prevent carcinogenesis in vivo.

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