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
Affiliations
- Zahra Erami
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- David Herrmann
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Sean C. Warren
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Max Nobis
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- Ewan J. McGhee
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- Morghan C. Lucas
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Wilfred Leung
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Nadine Reischmann
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Agata Mrowinska
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- Juliane P. Schwarz
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- Shereen Kadir
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- James R.W. Conway
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Claire Vennin
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Saadia A. Karim
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- Andrew D. Campbell
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- David Gallego-Ortega
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Astrid Magenau
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Kendelle J. Murphy
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Rachel A. Ridgway
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- Andrew M. Law
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Stacey N. Walters
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Shane T. Grey
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- David R. Croucher
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Lei Zhang
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Herbert Herzog
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- Edna C. Hardeman
- Neuromuscular and Regenerative Medicine Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
- Peter W. Gunning
- Oncology Research Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
- Christopher J. Ormandy
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- T.R. Jeffry Evans
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- Douglas Strathdee
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- Owen J. Sansom
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- Jennifer P. Morton
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- Kurt I. Anderson
- Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK
- Paul Timpson
- The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2010, Australia
- DOI
- https://doi.org/10.1016/j.celrep.2015.12.020
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 152 – 167
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.
Keywords
- intravital imaging
- FRAP
- E-cadherin
- Src-kinase
- pancreatic cancer
- invasion and metastasis
- cell adhesion and migration
- Kras
- p53
