Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue

E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mous...

Full description

Bibliographic Details
Main Authors: Zahra Erami, David Herrmann, Sean C. Warren, Max Nobis, Ewan J. McGhee, Morghan C. Lucas, Wilfred Leung, Nadine Reischmann, Agata Mrowinska, Juliane P. Schwarz, Shereen Kadir, James R.W. Conway, Claire Vennin, Saadia A. Karim, Andrew D. Campbell, David Gallego-Ortega, Astrid Magenau, Kendelle J. Murphy, Rachel A. Ridgway, Andrew M. Law, Stacey N. Walters, Shane T. Grey, David R. Croucher, Lei Zhang, Herbert Herzog, Edna C. Hardeman, Peter W. Gunning, Christopher J. Ormandy, T.R. Jeffry Evans, Douglas Strathdee, Owen J. Sansom, Jennifer P. Morton, Kurt I. Anderson, Paul Timpson
Format: Article
Language:English
Published: Elsevier 2016-01-01
Series:Cell Reports
Subjects:
p53
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124715014333
Description
Summary:E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology. We demonstrate the broad applications of this mouse by examining E-cadherin regulation in multiple tissues, including mammary, brain, liver, and kidney tissue, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment and gain insights into the dynamic remodeling of E-cadherin during in situ cancer progression. FRAP in the E-cadherin-GFP mouse, therefore, promises to be a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments.
ISSN:2211-1247