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

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.
AuthorsA 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
JournalOncogene (Oncogene) Vol. 31 Issue 12 Pg. 1493-503 (Mar 22 2012) ISSN: 1476-5594 [Electronic] England
PMID21822309 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fos
  • fos-related antigen 1
  • Receptor Protein-Tyrosine Kinases
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human
Topics
  • Cell Line, Tumor
  • Cell Movement (genetics)
  • Cell Proliferation
  • Cell Shape (drug effects)
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Phosphorylation
  • Proto-Oncogene Proteins (metabolism)
  • Proto-Oncogene Proteins c-fos (metabolism)
  • Receptor Protein-Tyrosine Kinases (metabolism)
  • Transcriptional Activation
  • Up-Regulation
  • Urinary Bladder Neoplasms (genetics)
  • Axl Receptor Tyrosine Kinase

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