Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL
Sayan, A. Emre, Stanford, R., Vickery, R., Grigorenko, E., Diesch, J., Kulbichi, K., Mellon, J. K., Edwards, Richard, Pal, R., Greaves, P., Jariel-Encontre, I., Piechaczyk, M., Kriajevska, M. and Dhillon, A. S. (2012) Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL. Oncogene, 31, (12), 1493-1503. (doi:10.1038/onc.2011.336). (PMID:21822309).
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Fos-related antigen 1 (Fra-1) is a Fos family member overexpressed in several types of human cancers. Here, we report that Fra-1 is highly expressed in the muscle-invasive form of the carcinoma of the bladder (80%) and to a lesser extent in superficial bladder cancer (42%). We demonstrate that in this type of cancer Fra-1 is regulated via a C-terminal instability signal and C-terminal phosphorylation. We show that manipulation of Fra-1 expression levels in bladder cancer cell lines affects cell morphology, motility and proliferation. The gene coding for AXL tyrosine kinase is directly upregulated by Fra-1 in bladder cancer and in other cell lines. Importantly, our data demonstrate that AXL mediates the effect of Fra-1 on tumour cell motility but not on cell proliferation. We suggest that AXL may represent an attractive therapeutic target in cancers expressing high Fra-1 levels
|Digital Object Identifier (DOI):||doi:10.1038/onc.2011.336|
|Keywords:||Fos-related antigen-1, cell motility, bladder cancer|
|Subjects:||R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
|Divisions:||Faculty of Medicine > Cancer Sciences
|Date Deposited:||25 May 2012 13:22|
|Last Modified:||31 Mar 2016 14:28|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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