Reference - Detail
| RRC ID | 32487 |
|---|---|
| Author | Macagno JP, Diaz Vera J, Yu Y, MacPherson I, Sandilands E, Palmer R, Norman JC, Frame M, Vidal M. |
| Title | FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells. |
| Journal | PLoS Genet |
| 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. |
| Volume | 10(3) |
| Pages | e1004262 |
| Published | 2014-3-1 |
| DOI | 10.1371/journal.pgen.1004262 |
| PII | PGENETICS-D-13-02823 |
| PMID | 24676055 |
| PMC | PMC3967952 |
| MeSH | Animals Breast Neoplasms / genetics* Breast Neoplasms / pathology Cell Line, Tumor Cell Proliferation Drosophila melanogaster / genetics Epithelial Cells / metabolism Female Focal Adhesion Kinase 1 / genetics* Focal Adhesion Kinase 1 / metabolism Humans MAP Kinase Signaling System / genetics* Phosphorylation Receptor Protein-Tyrosine Kinases / genetics* Receptor Protein-Tyrosine Kinases / metabolism |
| IF | 5.175 |
| Times Cited | 7 |
| WOS Category | GENETICS & HEREDITY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 4 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | DGRC#125903 |