Plakoglobin (γ-
catenin) is a homolog of β-
catenin with dual adhesive and signaling functions.
Plakoglobin participates in cell-cell adhesion as a component of the adherens junction and desmosomes whereas its signaling function is mediated by its interactions with various intracellular
protein partners. To determine the role of
plakoglobin during
tumorigenesis and
metastasis, we expressed
plakoglobin in the human tongue
squamous cell carcinoma (SCC9) cells and compared the
mRNA profiles of parental SCC9 cells and their
plakoglobin-expressing transfectants (SCC9-PG). We observed that the
mRNA levels of SATB1, the oncogenic chromatin remodeling factor, were decreased approximately 3-fold in SCC9-PG cells compared to parental SCC9 cells. Here, we showed that
plakoglobin decreased levels of SATB1
mRNA and
protein in SCC9-PG cells and that
plakoglobin and p53 associated with the SATB1 promoter.
Plakoglobin expression also resulted in decreased SATB1 promoter activity. These results were confirmed following
plakoglobin expression in the very low
plakoglobin expressing and invasive mammary
carcinoma cell line MDA-MB-231 cells (MDA-231-PG). In addition, knockdown of endogenous
plakoglobin in the non-invasive mammary
carcinoma MCF-7 cells (MCF-7-shPG) resulted in increased SATB1
mRNA and
protein.
Plakoglobin expression also resulted in increased
mRNA and
protein levels of the
metastasis suppressor Nm23-H1, a SATB1 target gene. Furthermore, the levels of various SATB1 target genes involved in
tumorigenesis and
metastasis were altered in MCF-7-shPG cells relative to parental MCF-7 cells. Finally,
plakoglobin expression resulted in decreased in vitro proliferation, migration and invasion in different
carcinoma cell lines. Together with the results of our previous studies, the data suggests that
plakoglobin suppresses
tumorigenesis and
metastasis through the regulation of genes involved in these processes.