Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse

Conway, J. R. W. et al. (2023) Monitoring AKT activity and targeting in live tissue and disease contexts using a real-time Akt-FRET biosensor mouse. Science Advances, 9(17), eadf9063. (doi: 10.1126/sciadv.adf9063) (PMID:37126544) (PMCID:PMC10132756)

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Abstract

Aberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessment of AKT activity using intravital imaging in conjunction with image stabilization and optical window technology. We demonstrate the sensitivity of the Akt-FRET biosensor mouse using various cancer models and verify its suitability to monitor response to drug targeting in spheroid and organotypic models. We also show that the dynamics of AKT activation can be monitored in real time in diverse tissues, including in individual islets of the pancreas, in the brown and white adipose tissue, and in the skeletal muscle. Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Morton, Professor Jen and Sansom, Professor Owen
Authors: Conway, J. R. W., Warren, S. C., Lee, Y.-K., McCulloch, A. T., Magenau, A., Lee, V., Metcalf, X. L., Stoehr, J., Haigh, K., Abdulkhalek, L., Guaman, C. S., Reed, D. A., Murphy, K. J., Pereira, B. A., Mélénec, P., Chambers, C., Latham, S. L., Lenthall, H., Deenick, E. K., Ma, Y., Phan, T., Lim, E., Joshua, A. M., Walters, S., Grey, S. T., Shi, Y.-C., Zhang, L., Herzog, H., Croucher, D. R., Philp, A., Scheele, C. L.G.J., Herrmann, D., Sansom, O. J., Morton, J. P., Papa, A., Haigh, J. J., Nobis, M., and Timpson, P.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Science Advances
Publisher:American Association for the Advancement of Science
ISSN:2375-2548
ISSN (Online):2375-2548
Published Online:26 April 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Science Advances 9(17): eadf9063
Publisher Policy:Reproduced under a Creative Commons License

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