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

被引：46

作者：

Erami, Zahra ^{[1
]}

Herrmann, David ^{[2
,3
]}

Warren, Sean C. ^{[2
,3
]}

Nobis, Max ^{[1
]}

McGhee, Ewan J. ^{[1
]}

Lucas, Morghan C. ^{[2
,3
]}

Leung, Wilfred ^{[2
,3
]}

Reischmann, Nadine ^{[2
,3
]}

Mrowinska, Agata ^{[1
]}

Schwarz, Juliane P. ^{[1
]}

Kadir, Shereen ^{[1
]}

Conway, James R. W. ^{[2
,3
]}

Vennin, Claire ^{[2
,3
]}

Karim, Saadia A. ^{[1
]}

Campbell, Andrew D. ^{[1
]}

Gallego-Ortega, David ^{[2
,3
]}

Magenau, Astrid ^{[2
,3
]}

Murphy, Kendelle J. ^{[2
,3
]}

Ridgway, Rachel A. ^{[1
]}

Law, Andrew M. ^{[2
,3
]}

Walters, Stacey N. ^{[2
,3
]}

Grey, Shane T. ^{[2
,3
]}

Croucher, David R. ^{[2
,3
]}

Zhang, Lei ^{[2
,3
]}

Herzog, Herbert ^{[2
,3
]}

Hardeman, Edna C. ^{[4
]}

Gunning, Peter W. ^{[5
]}

Ormandy, Christopher J. ^{[2
,3
]}

Evans, T. R. Jeffry ^{[1
]}

Strathdee, Douglas ^{[1
]}

Sansom, Owen J. ^{[1
]}

Morton, Jennifer P. ^{[1
]}

Anderson, Kurt I. ^{[1
]}

Timpson, Paul ^{[2
,3
]}

机构：

[1] Canc Res UK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland

[2] Univ New S Wales, Fac Med, St Vincents Clin Sch, Garvan Inst Med Res, Sydney, NSW 2010, Australia

[3] Univ New S Wales, Fac Med, St Vincents Clin Sch, Kinghorn Canc Ctr,Canc Div, Sydney, NSW 2010, Australia

[4] Univ New S Wales, Sch Med Sci, Neuromuscular & Regenerat Med Unit, Sydney, NSW 2052, Australia

[5] Univ New S Wales, Sch Med Sci, Oncol Res Unit, Sydney, NSW 2052, Australia

来源：

CELL REPORTS | 2016年 / 14卷 / 01期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; PANCREATIC DUCTAL ADENOCARCINOMA; MUTANT P53; LIVING CELLS; KINASE INHIBITOR; STEADY-STATE; CANCER; SRC; PROTEIN; INVASION;

D O I：

10.1016/j.celrep.2015.12.020

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：152 / 167

页数：16

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