FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Macagno, J. P., Diaz Vera, J., Yu, Y., MacPherson, I. , Sandilands, E., Palmer, R., Norman, J. C. , Frame, M. and Vidal, M. (2014) FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells. PLoS Genetics, 10(3), e1004262. (doi:10.1371/journal.pgen.1004262)

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Abstract

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Yu, Dr Yachuan and MacPherson, Dr Iain and Norman, Professor James and Diaz, Dr Jesica and Vidal, Dr Marcos and Macagno, Mr Juan
Authors: Macagno, J. P., Diaz Vera, J., Yu, Y., MacPherson, I., Sandilands, E., Palmer, R., Norman, J. C., Frame, M., and Vidal, M.
Subjects:Q Science > QH Natural history > QH301 Biology
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:PLoS Genetics
Publisher:Public Library of Science
ISSN:1553-7404
ISSN (Online):1553-7404
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in PLoS Genetics 10(3):e1004262
Publisher Policy:Reproduced under a Creative Commons License

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