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- Title
Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL.
- Authors
Sayan, A E; Stanford, R; Vickery, R; Grigorenko, E; Diesch, J; Kulbicki, K; Edwards, R; Pal, R; Greaves, P; Jariel-Encontre, I; Piechaczyk, M; Kriajevska, M; Mellon, J K; Dhillon, A S; Tulchinsky, E
- Abstract
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.
- Publication
Oncogene, 2012, Vol 31, Issue 12, p1493
- ISSN
1476-5594
- Publication type
Journal Article
- DOI
10.1038/onc.2011.336