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)

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

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Contributors

Author: A. Emre Sayan

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