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

by Diesch, J , Piechaczyk, M , Sayan, A E , Stanford, R , Dhillon, A S , Grigorenko, E , Vickery, R , Kulbicki, K , Edwards, R , Pal, R , Mellon, J K , Jariel-Encontre, I , Greaves, P , Kriajevska, M , Tulchinsky, E

in Antigens / Apoptosis / Axl protein / Biochemistry, Molecular Biology / Bladder / Bladder cancer / Cancer / Carcinoma / Care and treatment / Cell adhesion & migration / Cell Biology / Cell Line, Tumor / Cell migration / Cell Movement - genetics / Cell Proliferation / Cell Shape - drug effects / Cytology / Data processing / Fos protein / Fos-related antigen / Fra1 protein / Gene expression / Gene Expression Regulation, Neoplastic / Genetic aspects / Human Genetics / Humans / Internal Medicine / Invasiveness / Kinases / Life Sciences / Medicine / Medicine & Public Health / Motility / Oncology / original-article / Phosphorylation / Physiological aspects / Protein-tyrosine kinase / Protein-tyrosine kinase receptors / Proto-Oncogene Proteins - metabolism / Proto-Oncogene Proteins c-fos - metabolism / Receptor Protein-Tyrosine Kinases - metabolism / Therapeutic targets / Transcription / Transcriptional Activation / Tumor cell lines / Tumors / Tyrosine / Up-Regulation / Urinary bladder / Urinary Bladder Neoplasms - genetics

2012

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

2012

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

2012

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Journal Article

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

Diesch, J,

Piechaczyk, M,

Sayan, A E,

Stanford, R,

Dhillon, A S,

Grigorenko, E,

Vickery, R,

Kulbicki, K,

Edwards, R,

Pal, R,

Mellon, J K,

Jariel-Encontre, I,

Greaves, P,

Kriajevska, M,

Tulchinsky, E

2012

Overview

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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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Publishing Group [1987-....]

Subject

Antigens

/ Apoptosis

/ Axl protein

/ Biochemistry, Molecular Biology

/ Bladder

/ Bladder cancer

/ Cancer