Oncotarget

Research Papers:

ADAMTS1-mediated targeting of TSP-1 by PPARδ suppresses migration and invasion of breast cancer cells

Sun Ah Ham, Taesik Yoo, Won Jin Lee, Jung Seok Hwang, Jinwoo Hur, Kyung Shin Paek, Dae-Seog Lim, Sung Gu Han, Chi-Ho Lee and Han Geuk Seo _

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Oncotarget. 2017; 8:94091-94103. https://doi.org/10.18632/oncotarget.21584

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Abstract

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

Correspondence to:

Han Geuk Seo, email: hgseo@konkuk.ac.kr

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

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) 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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