Poster Presentation 28th Lorne Cancer Conference 2016

Intravital FRAP imaging using an E-cadherin-GFP mouse reveals disease and drug-dependent dynamic regulation of cell-cell junctions in live tissue  (#162)

David Herrmann 1 , Zahra Erami 2 , Sean C Warren 1 , Max Nobis 2 , Ewan J McGhee 2 , Morghan Lucas 1 , Wilfred Leung 1 , Nadine Reischmann 1 , Agata Mrowinska 2 , Juliane P Schwarz 2 , Shereen Kadir 2 , James RW Conway 1 , Claire Vennin 1 , Saadia A Karim 2 , Andrew D Campbell 2 , David Gallego-Ortega 1 , Astrid Magenau 1 , Kendelle J Murphy 1 , Rachel A Ridgway 2 , Andrew M Law 1 , Stacey N Walters 1 , Shane T Grey 1 , David Croucher 1 , Lei Zhang 1 , Herbert Herzog 1 , Edna C Hardeman 3 , Peter W Gunning 4 , Christopher J Ormandy 1 , Jeffry TR Evans 2 , Douglas Strathdee 2 , Owen J Sansom 2 , Jennifer P Morton 2 , Kurt I Anderson 2 , Paul Timpson 1
  1. Garvan Institute / The Kinghorn Cancer Centre, Darlinghurst, NSW, Australia
  2. Cancer Research UK Beatson Institute, Glasgow, UK
  3. Neuromuscular and Regenerative Medicine Unit, School of Medical Sciences, University of New South Wales, Sydney, Australia
  4. Oncology Research Unit, School of Medical Sciences, University of New South Wales, Sydney, Sydney, NSW, Australia

E-cadherin-mediated cell-cell junctions play a prominent role in maintaining 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 have generated an E-cadherin-GFP mouse, which enables intravital photobleaching and quantification of E-cadherin mobility in live tissue, without affecting normal biology. We demonstrate the broad applications of this mouse to examine E-cadherin regulation in multiple tissues including mammary, brain, liver and kidney, 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 reveal new 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 new tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments.