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

: Erami Z, Herrmann D, Warren SC, Nobis M, McGhee EJ, Lucas MC, Leung W, Reischmann N, Mrowinska A, Schwarz JP, Kadir S, Conway JRW, Vennin C, Karim SA, Campbell AD, Magenau A, Gallego-Ortega D, Ridgway RA, Murphy KJ, Walters SN, Law AM, Croucher DR, Grey ST, Herzog H, Zhang L, Gunning PW, Hardeman EC, Evans TRJ, Ormandy CJ, Sansom OJ, Strathdee D, Timpson P, Morton JP, Anderson KI

: 2016

: Cell Reports

: Cell reports

: Cell Rep

: 14

: 1

: 152

: 167

: 16

: 2211-1247

DOI: https://doi.org/10.1016/j.celrep.2015.12.020(external)

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.