ADAMTS1-mediated targeting of TSP-1 by PPAR? suppresses migration and invasion of breast cancer cells.

ABSTRACT: Migration and invasion of cancer cells into surrounding tissue is a key stage of cancer metastasis. Here, we show that peroxisome proliferator-activated receptor (PPAR) ? regulates migration and invasion of human breast cancer cells via thrombospondin-1 (TSP-1) and its degrading protease, a disintegrin and metalloprotease domains with thrombospondin motifs 1 (ADAMTS1). Activation of PPAR? by GW501516, a specific ligand for PPAR?, led to marked inhibition in the cell migration and TSP-1 expression of breast cancer. These effects were suppressed by small interfering RNA-mediated knock-down of ADAMTS1, indicating that ADAMTS1 is involved in PPAR?-mediated inhibition of migration and TSP-1 expression in breast cancer cells. In addition, ligand-activated PPAR? upregulated expression of ADAMTS1 at the transcriptional level via binding of PPAR? to a direct repeat-1 site within the ADAMTS1 gene promoter. Furthermore, ligand-activated PPAR? suppressed invasion of breast cancer cells in an ADAMTS1-dependent manner. Taken together, these results demonstrate that PPAR? suppresses migration and invasion of breast cancer cells by downregulating TSP-1 in a process mediated by upregulation of ADAMTS1.

SUBMITTER: Ham SA 

PROVIDER: S-EPMC5706858 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature