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Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL
journal contribution
posted on 2022-11-30, 02:54 authored by A E Sayan, R Stanford, R Vickery, E Grigorenko, J Diesch, K Kulbicki, R Edwards, R Pal, P Greaves, I Jariel-Encontre, M Piechaczyk, M Kriajevska, J K Mellon, Amardeep DhillonAmardeep Dhillon, E TulchinskyFos-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. © 2012 Macmillan Publishers Limited All rights reserved.
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Journal
OncogeneVolume
31Pagination
1493 - 1503Publisher DOI
ISSN
0950-9232eISSN
1476-5594Publication classification
C1.1 Refereed article in a scholarly journalUsage metrics
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