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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Authors | 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 |
Journal | Oncogene
(Oncogene)
Vol. 31
Issue 12
Pg. 1493-503
(Mar 22 2012)
ISSN: 1476-5594 [Electronic] England |
PMID | 21822309
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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