title: MEK-dependent IL-8 induction regulates the invasiveness of triple-negative breast cancer cells.
abstract: Interleukin-8 (IL-8) serves as a prognostic marker for breast cancer, and its expression level correlates with metastatic breast cancer and poor prognosis. Here, we investigated the levels of IL-8 expression in a variety of breast cancer cells and the regulatory mechanism of IL-8 in triple-negative breast cancer (TNBC) cells. Our results showed that IL-8 expression correlated positively with overall survival in basal-type breast cancer patients. The levels of IL-8 mRNA expression and protein secretion were significantly increased in TNBC cells compared with non-TNBC cells. In addition, the invasiveness of the TNBC cells was dramatically increased by IL-8 treatment and then augmented invasion-related proteins such as matrix metalloproteinase (MMP)-2 or MMP-9. We observed that elevated IL-8 mRNA expression and protein secretion were suppressed by a specific MEK1/2 inhibitor, UO126. In contrast, the overexpression of constitutively active MEK significantly increased the level of IL-8 mRNA expression in BT474 non-TNBC cells. Finally, we investigated the effect of UO126 on the tumorigenecity of TNBC cells. Our results showed that anchorage-independent growth, cell invasion, and cell migration were also decreased by UO126 in TNBC cells. As such, we demonstrated that IL-8 expression is regulated through MEK/ERK-dependent pathways in TNBC cells. A diversity of MEK blockers, including UO126, may be promising for treating TNBC patients.
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea. sangmin3005.kim@samsung.com.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea.
authors.forename: Myeongjin
authors.initials: M
authors.lastname: Jeon
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea.|Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea.
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea. sjnam@skku.edu.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002070:Butadienes / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D009570:Nitriles / Q000008:administration & dosage*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D002070:Butadienes; C508606:CXCL8 protein, human; D016209:Interleukin-8; D009570:Nitriles; C113580:U 0126; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C079843:inolimomab
keywords: Cell invasion; IL-8; MEK; Poor prognosis; Triple-negative breast cancer