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

Erami Rud Majani, Z. et al. (2016) Intravital FRAP imaging using an E-cadherin-GFP mouse reveals disease- and drug-dependent dynamic regulation of cell-cell junctions in live tissue. Cell Reports, 14(1), pp. 152-167. (doi: 10.1016/j.celrep.2015.12.020) (PMID:26725115)

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.

• Item Type: Articles
• Additional Information: P.T., D.H., S.C.W., M.C.L., W.L., N.R., J.R.W.C., C.V., D.G., A.M., K.J.M., A.M.L., D.R.C., and C.J.O. were funded by an NHMRC project grant, an ARC Future grant, a CINSW equipment grant, an Ainsworth Pancreatic Cancer Fellowship, Cancer Council NSW, and a Tour de Cure grant. K.I.A., Z.E., M.N., E.J.M., A.M., J.P.S., S.K., S.A.K., A.D.C., R.A.R., T.R.J.E., D.S., O.J.S., and J.P.M. were funded by a CRUK core grant.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kadir, Dr Shereen and Anderson, Professor Kurt and Timpson, Dr Paul and Mrowinska, Ms Agata and McGhee, Dr Ewan and Evans, Professor Jeff and Morton, Professor Jen and Strathdee, Mr Douglas and Ridgway, Dr Rachel and Karim, Ms Saadia and Erami Rud Majani, Mrs Zahra and Sansom, Professor Owen and Campbell, Dr Andrew
• Authors: Erami Rud Majani, Z., Herrmann, D., Warren, S. C., Nobis, M., McGhee, E. J., Lucas, M. C., Leung, W., Reischmann, N., Mrowinska, A., Schwarz, J. P., Kadir, S., Conway, J. R.W., Vennin, C., Karim, S. A., Campbell, A. D., Gallego-Ortega, D., Magenau, A., Murphy, K. J., Ridgway, R. A., Law, A. M., Walters, S. N., Grey, S. T., Croucher, D. R., Zhang, L., Herzog, H., Hardeman, E. C., Gunning, P. W., Ormandy, C. J., Evans, T.R. J., Strathdee, D., Sansom, O. J., Morton, J. P., Anderson, K. I., and Timpson, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Reports
• Publisher: Elsevier
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• First Published: In Cell Reports 14 (1), p152–167