title: Ligand-activated PPARδ modulates the migration and invasion of melanoma cells by regulating Snail expression.
abstract: Peroxisome proliferator-activated receptor (PPAR) δ is implicated in the carcinogenesis of several types of cancer. However, the therapeutic efficacy of PPARδ ligands against cancer progression is unclear. Here, we showed that PPARδ modulates the migration and invasion of melanoma cells by up-regulating Snail expression. Activation of PPARδ by GW501516, a specific ligand for PPARδ, significantly increased the migration and invasion of highly metastatic A375SM cells, but not that of low metastatic A375P cells. The migration- and invasion-promoting effects of PPARδ on A375SM cells was associated with increased Snail expression, which was accompanied by a decrease in E-cadherin expression. Furthermore, a significant concentration- and time-dependent increase in the levels of Snail mRNA and protein was observed in A375SM cells (but not A375P cells) treated with GW501516. The effects of GW501516 were almost completely abrogated by a small interfering RNA against PPARδ, suggesting that PPARδ mediates the effects of GW501516. Activation of PPARδ in SK-MEL-2 and SK-MEL-5 (but not SK-MEL-3) melanoma cell lines also led to significant increases in the expression of Snail mRNA and protein, which mirrored the invasive and migratory potential of these cell lines. These results suggest that PPARδ promotes the aggressive phenotype observed in highly metastatic melanoma cells by up-regulating Snail.
authors.affiliation: Department of Animal Biotechnology, Konkuk University 120 Neungdong-ro, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Ham
authors.affiliation: Department of Animal Biotechnology, Konkuk University 120 Neungdong-ro, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
authors.forename: Taesik
authors.initials: T
authors.lastname: Yoo
authors.affiliation: Department of Animal Biotechnology, Konkuk University 120 Neungdong-ro, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
authors.forename: Jung Seok
authors.initials: JS
authors.lastname: Hwang
authors.affiliation: Department of Animal Biotechnology, Konkuk University 120 Neungdong-ro, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Kang
authors.affiliation: Department of Animal Biotechnology, Konkuk University 120 Neungdong-ro, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
authors.forename: Won Jin
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Nursing, Semyung University 65 Semyung-ro, Jecheon 390-711, Republic of Korea.
authors.forename: Kyung Shin
authors.initials: KS
authors.lastname: Paek
authors.affiliation: Department of Animal Biotechnology, Konkuk University 120 Neungdong-ro, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
authors.forename: Chankyu
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Animal Biotechnology, Konkuk University 120 Neungdong-ro, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Animal Biotechnology, Konkuk University 120 Neungdong-ro, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Do
authors.affiliation: Department of Applied Bioscience, College of Life Science, CHA University 30 Beolmal-ro, Bundang-gu, Seongnam 463-712, Republic of Korea.
authors.forename: Dae-Seog
authors.initials: DS
authors.lastname: Lim
authors.affiliation: Department of Animal Biotechnology, Konkuk University 120 Neungdong-ro, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
keywords: PPARδ; Snail; invasion; melanoma; migration