| RRC ID |
32487
|
| 著者 |
Macagno JP, Diaz Vera J, Yu Y, MacPherson I, Sandilands E, Palmer R, Norman JC, Frame M, Vidal M.
|
| タイトル |
FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells.
|
| ジャーナル |
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.
|
| 巻・号 |
10(3)
|
| ページ |
e1004262
|
| 公開日 |
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
|
| 引用数 |
7
|
|
WOS 分野
|
GENETICS & HEREDITY
|
| リソース情報 |
| ショウジョウバエ |
DGRC#125903 |
