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

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.

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

publication date

  • 2012