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Role of the Fos family members, c-Fos, Fra-1 and Fra-2, in the regulation of cell motility

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Abstract

The AP-1 transcription factor is composed of members of the Fos, Jun and ATF families, and plays a key role in tumor progression. We investigated whether Fos proteins regulate cell motility, and if so, whether this capacity is related to their transactivation potential. Two cell lines with different expression profiles of AP-1 were employed focusing on the Fos-family members c-Fos, Fra-1 and Fra-2. Transactivation motifs are found in c-Fos, but not in Fra-1 or Fra-2. The adenocarcinoma CSML0 cells display a low motility and do not express Fra-1 or Fra-2, and only very little c-Fos. In contrast, the fibroblastoid L929 cells express both Fra-1 and Fra-2, but no c-Fos, and these cells display a high motility. Transfection with Fra-1 or c-Fos, but not with Fra-2, strongly enhanced the motility of CSML0 cells. The effect of Fra-1 required the presence of the N-terminal domain of this protein. Conversely, transfection with a Fos dominant-negative mutant or with anti-sense fra-1 or fra-2, strongly reduced the motility of L929 cells. Changes in cell motility correlated with the morphological appearance and the degree of contact with the substratum. We conclude that Fos proteins have distinct roles in the regulation of cell motility.

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Acknowledgements

This work was supported by grants from the Danish Cancer Society, the Danish Medical Research Council, the Danish Cancer Research Foundation, the Danish Natural Science Research Council, The John and Birthe Meyer Foundation and the Lundbeck Foundation.

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Author notes

  1. Eugene Tulchinsky

    Present address: University of Leicester, Division of Urology, Clinical Sciences Unit, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK

Authors and Affiliations

  1. Protein Laboratory, Institute of Molecular Pathology, School of Medicine, Copenhagen University, Copenhagen, DK-2200, Denmark

    Vadim Tkach, Elisabeth Bock & Vladimir Berezin

  2. Department of Molecular Cancer Biology, Institute of Cancer Biology, Danish Cancer Society, Copenhagen Ø, DK-2100, Denmark

    Eugene Tulchinsky & Eugene Lukanidin

  3. Laboratory of Metabolism, NCI, National Institutes of Health, Bethesda, 20892, MD, USA

    Charles Vinson

Authors
  1. Vadim Tkach
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  2. Eugene Tulchinsky
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  3. Eugene Lukanidin
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  4. Charles Vinson
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  5. Elisabeth Bock
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  6. Vladimir Berezin
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Correspondence to Vladimir Berezin.

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Tkach, V., Tulchinsky, E., Lukanidin, E. et al. Role of the Fos family members, c-Fos, Fra-1 and Fra-2, in the regulation of cell motility. Oncogene 22, 5045–5054 (2003). https://doi.org/10.1038/sj.onc.1206570

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