Metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes.
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.
Mahoney
My G
MG
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, PA 19107, USA. My.Mahoney@mail.tju.edu
Simpson
Anisha
A
Jost
Monika
M
Noé
Mariadele
M
Kari
Csaba
C
Pepe
Deanna
D
Choi
Yoo Won
YW
Uitto
Jouni
J
Rodeck
Ulrich
U
D023102:Anoikis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009362:Neoplasm Metastasis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; C089320:MTA1 protein, human; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D051020:bcl-X Protein; D066246:ErbB Receptors; D006655:Histone Deacetylases