Interleukin-18 enhances breast cancer cell migration via down-regulation of claudin-12 and induction of the p38 MAPK pathway

Yoolhee Yang, Soyoung Cheon, Min Kyung Jung, Seok Bean Song, Daejin Kim, Hee Jung Kim, Hyunjeong Park, Sa Ik Bang, Dae Ho Cho

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)379-386
Number of pages8
JournalBiochemical and biophysical research communications
Volume459
Issue number3
DOIs
Publication statusPublished - 2015 Apr 10
Externally publishedYes

Fingerprint

Interleukin-18
p38 Mitogen-Activated Protein Kinases
Cell Movement
Down-Regulation
Cells
Breast Neoplasms
MCF-7 Cells
Claudin-3
Claudin-4
Claudins
Claudin-1
Tight Junction Proteins
Neoplasms
Small Interfering RNA
Zonula Occludens-1 Protein
Phosphorylation
Mitogen-Activated Protein Kinases
Stomach Neoplasms
Tumors
Melanoma

Keywords

  • Breast cancer
  • Claudin-12
  • Interleukin-18 (IL-18)
  • Migration
  • Tight junction

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Interleukin-18 enhances breast cancer cell migration via down-regulation of claudin-12 and induction of the p38 MAPK pathway. / Yang, Yoolhee; Cheon, Soyoung; Jung, Min Kyung; Song, Seok Bean; Kim, Daejin; Kim, Hee Jung; Park, Hyunjeong; Bang, Sa Ik; Cho, Dae Ho.

In: Biochemical and biophysical research communications, Vol. 459, No. 3, 10.04.2015, p. 379-386.

Research output: Contribution to journalArticle

Yang, Yoolhee ; Cheon, Soyoung ; Jung, Min Kyung ; Song, Seok Bean ; Kim, Daejin ; Kim, Hee Jung ; Park, Hyunjeong ; Bang, Sa Ik ; Cho, Dae Ho. / Interleukin-18 enhances breast cancer cell migration via down-regulation of claudin-12 and induction of the p38 MAPK pathway. In: Biochemical and biophysical research communications. 2015 ; Vol. 459, No. 3. pp. 379-386.
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AU - Cheon, Soyoung

AU - Jung, Min Kyung

AU - Song, Seok Bean

AU - Kim, Daejin

AU - Kim, Hee Jung

AU - Park, Hyunjeong

AU - Bang, Sa Ik

AU - Cho, Dae Ho

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