title: 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.
authors.affiliation: Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Sayan
authors.forename: R
authors.initials: R
authors.lastname: Stanford
authors.forename: R
authors.initials: R
authors.lastname: Vickery
authors.forename: E
authors.initials: E
authors.lastname: Grigorenko
authors.forename: J
authors.initials: J
authors.lastname: Diesch
authors.forename: K
authors.initials: K
authors.lastname: Kulbicki
authors.forename: R
authors.initials: R
authors.lastname: Edwards
authors.forename: R
authors.initials: R
authors.lastname: Pal
authors.forename: P
authors.initials: P
authors.lastname: Greaves
authors.forename: I
authors.initials: I
authors.lastname: Jariel-Encontre
authors.forename: M
authors.initials: M
authors.lastname: Piechaczyk
authors.forename: M
authors.initials: M
authors.lastname: Kriajevska
authors.forename: J K
authors.initials: JK
authors.lastname: Mellon
authors.forename: A S
authors.initials: AS
authors.lastname: Dhillon
authors.forename: E
authors.initials: E
authors.lastname: Tulchinsky
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D048430:Cell Shape / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D000094963:Axl Receptor Tyrosine Kinase; D000099169:Fos-Related Antigen 1
chemical_list: D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; D000099169:Fos-Related Antigen 1; C000722289:AXL protein, human