ADAMTS1-mediated targeting of TSP-1 by PPARδ suppresses migration and invasion of breast cancer cells
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Sun Ah Ham1, Taesik Yoo1, Won Jin Lee1, Jung Seok Hwang1, Jinwoo Hur1, Kyung Shin Paek2, Dae-Seog Lim3, Sung Gu Han1, Chi-Ho Lee1 and Han Geuk Seo1
1Sanghuh College of Life Sciences, Konkuk University, Seoul 05029, Korea
2Department of Nursing, Semyung University, Jechon 27136, Korea
3Department of Biotechnology, CHA University, Seongnam 13488, Korea
Han Geuk Seo, email: firstname.lastname@example.org
Keywords: a disintegrin and metalloprotease domains with thrombospondin motifs 1, breast cancer cells, metastasis, peroxisome proliferator-activated receptor δ, thrombospondin-1
Received: July 04, 2017 Accepted: September 21, 2017 Published: October 06, 2017
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) δ 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 PPARδ by GW501516, a specific ligand for PPARδ, 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 PPARδ-mediated inhibition of migration and TSP-1 expression in breast cancer cells. In addition, ligand-activated PPARδ upregulated expression of ADAMTS1 at the transcriptional level via binding of PPARδ to a direct repeat-1 site within the ADAMTS1 gene promoter. Furthermore, ligand-activated PPARδ suppressed invasion of breast cancer cells in an ADAMTS1-dependent manner. Taken together, these results demonstrate that PPARδ suppresses migration and invasion of breast cancer cells by downregulating TSP-1 in a process mediated by upregulation of ADAMTS1.
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