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

作者信息

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

机构信息

Cancer Research UK Beatson Institute, Garscube Estate, Glasgow, United Kingdom.

Edinburgh Cancer Research UK Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom.

出版信息

PLoS Genet. 2014 Mar 27;10(3):e1004262. doi: 10.1371/journal.pgen.1004262. eCollection 2014 Mar.

DOI:10.1371/journal.pgen.1004262
PMID:24676055
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3967952/
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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/cdb1bfc0c8c4/pgen.1004262.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/d617fc2d54eb/pgen.1004262.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/7615bcaa1f33/pgen.1004262.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/2a2ef1bb38b2/pgen.1004262.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/caa7daebb9ab/pgen.1004262.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/e7e9cbd4c4fe/pgen.1004262.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/71d4382c3d92/pgen.1004262.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/b313147405ec/pgen.1004262.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/cdb1bfc0c8c4/pgen.1004262.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/d617fc2d54eb/pgen.1004262.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/7615bcaa1f33/pgen.1004262.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/2a2ef1bb38b2/pgen.1004262.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/caa7daebb9ab/pgen.1004262.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/e7e9cbd4c4fe/pgen.1004262.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/71d4382c3d92/pgen.1004262.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/b313147405ec/pgen.1004262.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bfac/3967952/cdb1bfc0c8c4/pgen.1004262.g008.jpg

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