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Ham SA, Yoo T, Hwang JS, et al. Ligand-activated PPARδ modulates the migration and invasion of melanoma cells by regulating Snail expression. Am J Cancer Res. 2014;4(6):674-82
Ham, S. A., Yoo, T., Hwang, J. S., Kang, E. S., Lee, W. J., Paek, K. S., Park, C., Kim, J. H., Do, J. T., Lim, D. S., & Seo, H. G. (2014). Ligand-activated PPARδ modulates the migration and invasion of melanoma cells by regulating Snail expression. American journal of cancer research, 4(6), 674-82.
Ham, Sun Ah, et al. "Ligand-activated PPARδ modulates the migration and invasion of melanoma cells by regulating Snail expression." American journal of cancer research vol. 4,6 (2014): 674-82.
Ham SA, Yoo T, Hwang JS, Kang ES, Lee WJ, Paek KS, Park C, Kim JH, Do JT, Lim DS, Seo HG. Ligand-activated PPARδ modulates the migration and invasion of melanoma cells by regulating Snail expression. Am J Cancer Res. 2014 Nov 19;4(6):674-82. eCollection 2014. PMID: 25520859; PMCID: PMC4266703.
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Am J Cancer Res. 2014 Nov 19;4(6):674-82. eCollection 2014.

Ligand-activated PPARδ modulates the migration and invasion of melanoma cells by regulating Snail expression.

American journal of cancer research

Sun Ah Ham, Taesik Yoo, Jung Seok Hwang, Eun Sil Kang, Won Jin Lee, Kyung Shin Paek, Chankyu Park, Jin-Hoi Kim, Jeong Tae Do, Dae-Seog Lim, Han Geuk Seo

Affiliations

  1. Department of Animal Biotechnology, Konkuk University 120 Neungdong-ro, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
  2. Department of Nursing, Semyung University 65 Semyung-ro, Jecheon 390-711, Republic of Korea.
  3. Department of Applied Bioscience, College of Life Science, CHA University 30 Beolmal-ro, Bundang-gu, Seongnam 463-712, Republic of Korea.

PMID: 25520859 PMCID: PMC4266703

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.

Keywords: PPARδ; Snail; invasion; melanoma; migration

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