Research Papers:

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 and Daeho Cho _

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Oncotarget. 2016; 7:65825-65836. https://doi.org/10.18632/oncotarget.11669

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Joohyun Lee1,*, Kyung Eun Kim2,*, Soyoung Cheon1,*, Ju Han Song3, Younkyung Houh1, Tae Sung Kim3, Minchan Gil2, Kyung Jin Lee4, Seonghan Kim5, Daejin Kim5, Dae Young Hur5, Yoolhee Yang6, Sa Ik Bang6, Hyun Jeong Park7**, Daeho Cho1,2,**

1Department of Life Systems, Sookmyung Women’s University, Yongsan-ku, Seoul 140-742, Republic of Korea

2Department of Cosmetic Sciences, Sookmyung Women’s University, Yongsan-ku, Seoul 140-742, Republic of Korea

3Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seongbuk-gu, Seoul 02841, Republic of Korea

4Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea

5Department of Anatomy, Inje University College of Medicine, Busan, 614-735, Republic of Korea

6Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea

7Department of Dermatology, Yeouido St. Mary’s Hospital, The Catholic University of Korea, Seoul 150-713, Republic of Korea

*These authors have contributed equally to this work

**Co-corresponding authors: Daeho Cho and Hyun Jeong Park contribute to this work equally

Correspondence to:

Daeho Cho, email: [email protected]

Hyun Jeong Park, email: [email protected]

Keywords: interleukin-32, melanoma, migration, Erk1/2, E-cadherin

Received: August 09, 2015    Accepted: August 20, 2016    Published: August 29, 2016


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.

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