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Critical regulation of genes for tumor cell migration by AP-1

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Abstract

The AP-1 transcription factor plays a critical role in regulating tumor cell proliferation and has been implicated in controlling a program of gene expression that mediates cell motility and invasion in vitro. We have utilized two dominant negative AP-1 constructs, TAM67 and aFos, each fused to GFP, to investigate the role of AP-1 complexes in an invasive, clinically derived human tumor cell line, HT-1080. As expected, high levels of both GFP-TAM67 and GFP-aFos arrested HT-1080 cells in the G1 phase of the cell cycle. Strikingly, at low levels GFP-aFos, but not GFP-TAM67, caused a change in colony morphology, impairment of directional motility in a monolayer wound healing assay, as well as inhibition of chemotaxis and haptotaxis. Microarray analysis identified a novel set of AP-1 target genes, including the tumor suppressor TSCL-1 and regulators of actin cytoskeletal dynamics, including the gelsolin-like actin capping protein CapG. The demonstration that AP-1 regulates the expression of genes involved in tumor cell motility and cytoskeletal dynamics in a clinically derived human tumor cell line identifies new pathways of control for tumor cell motility.

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Authors and Affiliations

  1. Department of Cell Biology, Neurobiology and Anatomy, Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati College of Medicine University of Cincinnati, Cincinnati, Ohio, USA

    El Mustapha Bahassi & Robert F. Hennigan

  2. Division of Toxicology, University of Cincinnati College of Medicine University of Cincinnati, Cincinnati, Ohio, USA

    Saikumar Karyala & Craig R. Tomlinson

  3. Division of Biostatistics and Center for Genome Information, University of Cincinnati College of Medicine University of Cincinnati, Cincinnati, Ohio, USA

    Maureen A. Sartor

  4. Center for Genome Information, University of Cincinnati College of Medicine University of Cincinnati, Cincinnati, Ohio, USA

    Mario Medvedovic

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  1. El Mustapha Bahassi
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  2. Saikumar Karyala
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  4. Maureen A. Sartor
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  6. Robert F. Hennigan
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Bahassi, E.M., Karyala, S., Tomlinson, C.R. et al. Critical regulation of genes for tumor cell migration by AP-1. Clin Exp Metastasis 21, 293–304 (2004). https://doi.org/10.1023/B:CLIN.0000046132.46946.dd

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