title: Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue.
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.
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Erami
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Herrmann
authors.affiliation: 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.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Warren
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Max
authors.initials: M
authors.lastname: Nobis
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Ewan J
authors.initials: EJ
authors.lastname: McGhee
authors.affiliation: 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.
authors.forename: Morghan C
authors.initials: MC
authors.lastname: Lucas
authors.affiliation: 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.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Leung
authors.affiliation: 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.
authors.forename: Nadine
authors.initials: N
authors.lastname: Reischmann
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Agata
authors.initials: A
authors.lastname: Mrowinska
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Juliane P
authors.initials: JP
authors.lastname: Schwarz
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Shereen
authors.initials: S
authors.lastname: Kadir
authors.affiliation: 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.
authors.forename: James R W
authors.initials: JRW
authors.lastname: Conway
authors.affiliation: 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.
authors.forename: Claire
authors.initials: C
authors.lastname: Vennin
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Saadia A
authors.initials: SA
authors.lastname: Karim
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Campbell
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Gallego-Ortega
authors.affiliation: 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.
authors.forename: Astrid
authors.initials: A
authors.lastname: Magenau
authors.affiliation: 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.
authors.forename: Kendelle J
authors.initials: KJ
authors.lastname: Murphy
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Ridgway
authors.affiliation: 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.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Law
authors.affiliation: 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.
authors.forename: Stacey N
authors.initials: SN
authors.lastname: Walters
authors.affiliation: 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.
authors.forename: Shane T
authors.initials: ST
authors.lastname: Grey
authors.affiliation: 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.
authors.forename: David R
authors.initials: DR
authors.lastname: Croucher
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.affiliation: Neuromuscular and Regenerative Medicine Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Edna C
authors.initials: EC
authors.lastname: Hardeman
authors.affiliation: Oncology Research Unit, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gunning
authors.affiliation: 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.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ormandy
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: T R Jeffry
authors.initials: TRJ
authors.lastname: Evans
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Douglas
authors.initials: D
authors.lastname: Strathdee
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Sansom
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Morton
authors.affiliation: Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK. Electronic address: k.anderson@beatson.gla.ac.uk.
authors.forename: Kurt I
authors.initials: KI
authors.lastname: Anderson
authors.affiliation: 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. Electronic address: p.timpson@garvan.org.au.
authors.forename: Paul
authors.initials: P
authors.lastname: Timpson
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D061848:Optical Imaging / Q000379:methods*; D009928:Organ Specificity; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D016159:Tumor Suppressor Protein p53; D049452:Green Fluorescent Proteins; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)
keywords: E-cadherin; FRAP; Kras; Src-kinase; cell adhesion and migration; intravital imaging; invasion and metastasis; p53; pancreatic cancer