Intravital FRAP imaging using an E-cadherin-GFP mouse reveals disease- and drug-dependent dynamic regulation of cell-cell junctions in live tissue
Authors list
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 RW 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 TR Jeffry Evans Douglas Strathdee Owen J Sansom Jennifer P Morton Kurt Anderson Paul Timpson Toggle all authors (34)
Abstract
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.
Journal details
Journal Cell Reports
Volume 14
Issue number 1
Pages 152-167
Available online
Publication date
Full text links
Publisher website (DOI) 10.1016/j.celrep.2015.12.020
Europe PubMed Central 26725115
Pubmed 26725115
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