PMID- 25727011 OWN - NLM STAT- MEDLINE DCOM- 20150622 LR - 20220408 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 459 IP - 3 DP - 2015 Apr 10 TI - Interleukin-18 enhances breast cancer cell migration via down-regulation of claudin-12 and induction of the p38 MAPK pathway. PG - 379-86 LID - S0006-291X(15)00348-4 [pii] LID - 10.1016/j.bbrc.2015.02.108 [doi] AB - Interleukin-18 (IL-18) was recently reported to have a pro-tumor effect in various cancers. Increased IL-18 levels in the serum of cancer patients correlated with malignancy, and IL-18 acts a crucial factor for cell migration in gastric cancer and melanoma. Claudins, which are the most important tight junction proteins, are also linked with cancer progression and metastasis. However, the relationship between claudins and IL-18 is not well-understood. Here, we show that the migratory ability of MCF-7 cells was reduced when endogenous IL-18 expression was inhibited with IL-18 siRNA. Moreover, exogenous IL-18 enhanced breast cancer cell migration and suppressed the expression of the tight junction proteins claudin-1, claudin-3, claudin-4, and claudin-12 in MCF-7 cells. Knockdown of claudin-3, claudin-4, and claudin-12, but not claudin-1, increased breast cancer migration with maximal effects observed in claudin-12 siRNA-transfected cells. To investigate whether the mitogen-activated protein kinase (MAPK) signaling pathway is involved in IL-18-induced cell migration and claudin-12 expression, cells were pretreated with SB203580 (an inhibitor of p38 MAPK) or PD98059 (an inhibitor of ERK1/2) prior to the addition of IL-18. Although pretreatment of MCF-7 cells with SB203580 blocked both the enhanced cell migration and the decreased claudin-12 expression, PD98059 only blocked cell migration and did not affect claudin-12 expression. In addition, exogenous IL-18 induced rapid phosphorylation of p38 MAPK. These results suggest that IL-18 is an important factor inducing breast cancer cell migration through down-regulation of claudin-12 and activation of the p38 MAPK pathway. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Yang, Yoolhee AU - Yang Y AD - Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. FAU - Cheon, Soyoung AU - Cheon S AD - Department of Life Science, Sookmyung Women's University, Seoul, Republic of Korea. FAU - Jung, Min Kyung AU - Jung MK AD - Department of Life Science, Sookmyung Women's University, Seoul, Republic of Korea. FAU - Song, Seok Bean AU - Song SB AD - Department of Life Science, Sookmyung Women's University, Seoul, Republic of Korea. FAU - Kim, Daejin AU - Kim D AD - Department of Anatomy, College of Medicine, Chung Ang University, Seoul, Republic of Korea. FAU - Kim, Hee Jung AU - Kim HJ AD - Department of Dermatology, St Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Park, Hyunjeong AU - Park H AD - Department of Dermatology, St Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Bang, Sa Ik AU - Bang SI AD - Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: si55.bang@samsung.com. FAU - Cho, Daeho AU - Cho D AD - Department of Life Science, Sookmyung Women's University, Seoul, Republic of Korea. Electronic address: cdhkor@sookmyung.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150227 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (CLDN1 protein, human) RN - 0 (CLDN12 protein, human) RN - 0 (CLDN3 protein, human) RN - 0 (CLDN4 protein, human) RN - 0 (Claudin-1) RN - 0 (Claudin-3) RN - 0 (Claudin-4) RN - 0 (Claudins) RN - 0 (Flavonoids) RN - 0 (Imidazoles) RN - 0 (Interleukin-18) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyridines) RN - 0 (RNA, Small Interfering) RN - 0 (Recombinant Proteins) RN - OU13V1EYWQ (SB 203580) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Breast Neoplasms/genetics/*pathology/*physiopathology MH - Cell Line, Tumor MH - Cell Movement/drug effects/genetics/physiology MH - Claudin-1/antagonists & inhibitors/genetics/physiology MH - Claudin-3/antagonists & inhibitors/genetics/physiology MH - Claudin-4/antagonists & inhibitors/genetics/physiology MH - Claudins/antagonists & inhibitors/genetics/*physiology MH - Down-Regulation/drug effects MH - Female MH - Flavonoids/pharmacology MH - Gene Knockdown Techniques MH - Humans MH - Imidazoles/pharmacology MH - Interleukin-18/antagonists & inhibitors/genetics/*physiology MH - *MAP Kinase Signaling System/drug effects MH - MCF-7 Cells MH - Protein Kinase Inhibitors/pharmacology MH - Pyridines/pharmacology MH - RNA, Small Interfering/genetics MH - Recombinant Proteins/pharmacology MH - Tight Junctions/drug effects/physiology OTO - NOTNLM OT - Breast cancer OT - Claudin-12 OT - Interleukin-18 (IL-18) OT - Migration OT - Tight junction EDAT- 2015/03/03 06:00 MHDA- 2015/06/24 06:00 CRDT- 2015/03/03 06:00 PHST- 2015/02/13 00:00 [received] PHST- 2015/02/19 00:00 [accepted] PHST- 2015/03/03 06:00 [entrez] PHST- 2015/03/03 06:00 [pubmed] PHST- 2015/06/24 06:00 [medline] AID - S0006-291X(15)00348-4 [pii] AID - 10.1016/j.bbrc.2015.02.108 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2015 Apr 10;459(3):379-86. doi: 10.1016/j.bbrc.2015.02.108. Epub 2015 Feb 27.