FAK Acts as a Suppressor of RTK-MAP Kinase Signalling in Drosophila melanogaster Epithelia and Human Cancer Cells

Juan Pablo Macagno, Jesica Diaz Vera, Yachuan Yu, Iain Macpherson, Emma Sandilands, Ruth Palmer, Jim C Norman, Margaret Frame, Marcos Vidal

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Article numbere1004262
JournalPLoS Genetics
Volume10
Issue number3
Early online date27 Mar 2014
DOIs
Publication statusPublished - 27 Mar 2014

Fingerprint

Dive into the research topics of 'FAK Acts as a Suppressor of RTK-MAP Kinase Signalling in Drosophila melanogaster Epithelia and Human Cancer Cells'. Together they form a unique fingerprint.

Cite this