title: Interleukin-32α induces migration of human melanoma cells through downregulation of E-cadherin.
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.
authors: Department of Life Systems, Sookmyung Women's University, Yongsan-ku, Seoul 140-742, Republic of Korea.
authors: Joohyun
authors: J
authors: Lee
authors: Department of Cosmetic Sciences, Sookmyung Women's University, Yongsan-ku, Seoul 140-742, Republic of Korea.
authors: Kyung Eun
authors: KE
authors: Kim
authors: Department of Life Systems, Sookmyung Women's University, Yongsan-ku, Seoul 140-742, Republic of Korea.
authors: Soyoung
authors: S
authors: Cheon
authors: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seongbuk-gu, Seoul 02841, Republic of Korea.
authors: Ju Han
authors: JH
authors: Song
authors: Department of Life Systems, Sookmyung Women's University, Yongsan-ku, Seoul 140-742, Republic of Korea.
authors: Younkyung
authors: Y
authors: Houh
authors: Division of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seongbuk-gu, Seoul 02841, Republic of Korea.
authors: Tae Sung
authors: TS
authors: Kim
authors: Department of Cosmetic Sciences, Sookmyung Women's University, Yongsan-ku, Seoul 140-742, Republic of Korea.
authors: Minchan
authors: M
authors: Gil
authors: Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
authors: Kyung Jin
authors: KJ
authors: Lee
authors: Department of Anatomy, Inje University College of Medicine, Busan, 614-735, Republic of Korea.
authors: Seonghan
authors: S
authors: Kim
authors: Department of Anatomy, Inje University College of Medicine, Busan, 614-735, Republic of Korea.
authors: Daejin
authors: D
authors: Kim
authors: Department of Anatomy, Inje University College of Medicine, Busan, 614-735, Republic of Korea.
authors: Dae Young
authors: DY
authors: Hur
authors: Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors: Yoolhee
authors: Y
authors: Yang
authors: Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Republic of Korea.
authors: Sa Ik
authors: SI
authors: Bang
authors: Department of Dermatology, Yeouido St. Mary's Hospital, The Catholic University of Korea, Seoul 150-713, Republic of Korea.
authors: Hyun Jeong
authors: HJ
authors: Park
authors: Department of Life Systems, Sookmyung Women's University, Yongsan-ku, Seoul 140-742, Republic of Korea.|Department of Cosmetic Sciences, Sookmyung Women's University, Yongsan-ku, Seoul 140-742, Republic of Korea.
authors: Daeho
authors: D
authors: Cho
mesh_terms: D000818:Animals; D015703:Antigens, CD; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; C496971:IL32 protein, human; D007378:Interleukins; D020928:Mitogen-Activated Protein Kinases
keywords: E-cadherin; Erk1/2; interleukin-32; melanoma; migration