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Metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes

Oncogene volume 21, pages 2161–2170 (2002)Cite this article

Abstract

The human metastasis-associated gene (MTA1), a member of the nucleosome remodeling complex with histone deacetylase activity, is frequently overexpressed in biologically aggressive epithelial neoplasms. Here, we extend this observation to squamous carcinoma cells, which express high levels of MTA1 relative to normal or immortalized keratinocytes. To address functional aspects of MTA1 expression, we established variants of human immortalized keratinocytes (HaCaT cells) by expressing MTA1 cDNA in both the sense and antisense orientations. We demonstrate that (1) forced MTA1 expression enhances migration and invasion of immortalized keratinocytes; (2) MTA1 expression is necessary but not sufficient for cell survival in the anchorage independent state; (3) MTA1 contributes to expression of the anti-apoptotic Bcl-2 family member Bcl-xL; (4) MTA1 expression in immortalized keratinocytes depends, in part, on activation of the epidermal growth factor receptor (EGFR). These results establish that, in keratinocytes, MTA1 expression contributes to several aspects of the metastatic phenotype including survival in the anchorage independent state, migration, and invasion.

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Abbreviations

EGFR:

epidermal growth factor receptor

MTA1:

metastasis-associated protein 1

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Acknowledgements

We thank Dr PJ Jensen (University of Pennsylvania, Philadelphia, PA, USA) for primary keratinocytes, Dr N Fusenig for HaCaT keratinocytes, and Dr J Rheinwald for squamous carcinoma cells. This work was supported by grants from the National Institutes of Health and the Dermatology Foundation to U Rodeck and MG Mahoney, respectively. MG Mahoney is a recipient of a Career Development Award from the Dermatology Foundation.

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Authors and Affiliations

  1. Department of Dermatology and Cutaneous Biology, Jefferson Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania, PA, USA

    Mỹ G Mahoney, Anisha Simpson, Monika Jost, Mariadele Noé, Csaba Kari, Deanna Pepe, Yoo Won Choi, Jouni Uitto & Ulrich Rodeck

  2. Department of Biochemistry and Molecular Pharmacology, Jefferson Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, 19107, Pennsylvania, PA, USA

    Jouni Uitto

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  1. Mỹ G Mahoney
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Correspondence to Mỹ G Mahoney.

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Mahoney, M., Simpson, A., Jost, M. et al. Metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes. Oncogene 21, 2161–2170 (2002). https://doi.org/10.1038/sj.onc.1205277

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