Interleukin-32α induces migration of human melanoma cells through downregulation of E-cadherin
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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
Daeho Cho, email: firstname.lastname@example.org
Hyun Jeong Park, email: email@example.com
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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