Cell Reports (Jan 2016)

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

  • 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

DOI
https://doi.org/10.1016/j.celrep.2015.12.020
Journal volume & issue
Vol. 14, no. 1
pp. 152 – 167

Abstract

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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.

Keywords