Fra-1 controls motility of bladder cancer cells via transcriptional upregulation of the receptor tyrosine kinase AXL

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, A. S. Dhillon, E. Tulchinsky

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1493-1503
Number of pages11
JournalOncogene
Volume31
Issue number12
DOIs
Publication statusPublished - Mar 22 2012
Externally publishedYes

Keywords

  • bladder cancer
  • cell motility
  • Fos-related antigen-1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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