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Title: Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL.
Authors: Sayan, AE
Stanford, R
Vickery, R
Grigorenko, E
Diesch, J
Kulbicki, K
Edwards, R
Pal, R
Greaves, P
Jariel-Encontre, I
Piechaczyk, M
Kriajevska, M
Mellon, JK
Dhillon, AS
Tulchinsky, E
First Published: 22-Mar-2012
Citation: ONCOGENE, 2012, 31 (12), pp. 1493-1503
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.
DOI Link: 10.1038/onc.2011.336
eISSN: 1476-5594
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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