Interleukin-32α induces migration of human melanoma cells through downregulation of E-cadherin

Joohyun Lee, Kyung Eun Kim, Soyoung Cheon, Ju Han Song, Younkyung Houh, Tae Sung Kim, Minchan Gil, Kyung Jin Lee, Seonghan Kim, Daejin Kim, Dae Young Hur, Yoolhee Yang, Sa Ik Bang, Hyun Jeong Park, Dae Ho Cho

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Interleukin (IL)-32α, the shortest isoform of proinflammatory cytokine IL- 32, is associated with various inflammatory diseases and cancers. However, its involvement in human melanoma is not understood. To determine the effect of IL- 32α in melanoma, IL-32α levels were examined in human melanoma cell lines that exhibit different migratory abilities. IL-32α levels were higher in human melanoma cell lines with more migratory ability. An IL-32α-overexpressing G361 human melanoma cell line was generated to investigate the effect of IL-32α on melanoma migration. IL-32α-overexpressing G361 cells (G361-IL-32α) exhibit an increased migratory ability compared to vector control cells (G361-vector). To identify factors involved in IL-32α-induced migration, we compared expression of E-cadherin in G361-vector and G361-IL-32α cells. We observed decreased levels of E-cadherin in G361-IL-32α cells, resulting in F-actin polymerization. To further investigate signaling pathways related to IL-32α-induced migration, we treated G361-vector and G361-IL-32α cells with PD98059, a selective MEK inhibitor. Inhibition of Erk1/2 by PD98059 restored E-cadherin expression and decreased IL-32α-induced migration. In addition, cell invasiveness of G361-IL-32α cells was tested using an in vivo lung metastasis model. As results, lung metastasis was significantly increased by IL-32α overexpression. Taken together, these data indicate that IL-32α induced human melanoma migration via Erk1/2 activation, which repressed E-cadherin expression. Our findings suggest that IL-32α is a novel regulator of migration in melanoma.

Original languageEnglish
Pages (from-to)65825-65836
Number of pages12
JournalOncotarget
Volume7
Issue number40
DOIs
Publication statusPublished - 2016

Keywords

  • E-cadherin
  • Erk1/2
  • Interleukin-32
  • Melanoma
  • Migration

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Lee, J., Kim, K. E., Cheon, S., Song, J. H., Houh, Y., Kim, T. S., Gil, M., Lee, K. J., Kim, S., Kim, D., Hur, D. Y., Yang, Y., Bang, S. I., Park, H. J., & Cho, D. H. (2016). Interleukin-32α induces migration of human melanoma cells through downregulation of E-cadherin. Oncotarget, 7(40), 65825-65836. https://doi.org/10.18632/oncotarget.11669