title: Role of TOPK in lipopolysaccharide-induced breast cancer cell migration and invasion.
abstract: Inflammation has been known to be linked to invasion or metastasis of breast cancer, which has poor prognosis, although the regulatory mechanism remains to be undiscovered. Here we show that T-LAK cell-originated protein kinase (TOPK) mediates pro-inflammatory endotoxin lipopolysaccharide (LPS)-induced breast cancer cell migration and invasion. The mRNA or protein level of TOPK, toll- like receptor4 (TLR4), interleukin (IL)-6, vascular endothelial growth factor (VEGF) or matrix metalloproteinase9 (MMP9) genes related to TLR4 signaling or tumor progression was induced by LPS treatment in MCF7 breast cancer cells, but the induction was abolished by stable knocking down of TOPK in MCF7 cells. Also, TOPK depletion decreased LPS-induced phosphorylation of p38, but not ERK and JNK among mitogen-activated protein kinases (MAPKs). On the other hand, we revealed that TOPK is essential for transcriptional activity of NF-κB or MMP9 promoter triggered by LPS. The induced promoter activity of NF-κB or MMP9 but not AP-1 was inhibited by knocking down of TOPK. Furthermore, we demonstrated that inhibitor of TOPK or MMP9 as well as MMP9 siRNA efficiently blocked LPS-induced migration or invasion of breast cancer cell lines. Interestingly, both of expression of TOPK and TLR4 were markedly increased in high-grade breast cancer. Collectively, we conclude that TOPK functions as a key mediator of LPS/TLR4-induced breast cancer cell migration and invasion through regulation of MMP9 expression or activity, implying a potential role of TOPK as a therapeutic target linking LPS-induced inflammation to breast cancer development.
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Min-Ah
authors.initials: MA
authors.lastname: Seol
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Jung-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Anatomy, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Ji Heun
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Medical Science, Konyang University, Daejeon, Korea.
authors.forename: Jungmook
authors.initials: J
authors.lastname: Lyu
authors.affiliation: Department of Anatomy, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Seung Yun
authors.initials: SY
authors.lastname: Han
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Sang-Muk
authors.initials: SM
authors.lastname: Oh
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D061986:MCF-7 Cells; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase
keywords: TOPK; breast cancer; invasion; matrix metalloproteinase