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

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

Correspondence to: M G Mahoney, Department of Dermatology and Cutaneous Biology, 233 S. 10th St., Room 419 BLSB, Jefferson Medical College, Philadelphia, PA 19107, USA; E-mail: My.Mahoney@mail.tju.edu

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-x_L; (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.

Oncogene (2002) 21, 2161-2170 DOI: 10.1038/sj/onc/1205277

anoikis; epidermal growth factor; epithelial cells

EGFR, epidermal growth factor receptor; MTA1, metastasis-associated protein 1