title: By inhibiting Ras/Raf/ERK and MMP-9, knockdown of EpCAM inhibits breast cancer cell growth and metastasis.
abstract: Epithelial cell adhesion molecule (EpCAM) is a type I transmembrane protein that is expressed in the majority of normal epithelial tissues and is overexpressed in most epithelial cancers including breast cancer, where it plays an important role in cancer progression. However, the mechanism by which EpCAM promotes the progression of breast cancer is not understood. In this study, we found that EpCAM expression was increased in tumor tissue from breast cancer patients compared to healthy patients. Overexpression of EpCAM in breast cancer cells enhanced tumor cell growth in vitro and increased invasiveness, whereas small interfering RNA-mediated silencing of EpCAM (si-EpCAM) had the opposite effect. EpCAM knockdown led to decreased phosphorylation of Raf and ERK, suppression of malignant behavior of breast cancer cells, and inhibition of the Ras/Raf/ERK signaling pathway. Furthermore, si-EpCAM-mediated invasion and metastasis of breast carcinoma cells required the downregulation of matrix metalloproteinase-9 (MMP-9) through inhibition of this signaling pathway. In conclusion, our data show that knockdown of EpCAM can inhibition breast cancer cell growth and metastasis via inhibition of the Ras/Raf/ERK signaling pathway and MMP-9.
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, People's Republic of China.
authors.forename: Jiujiao
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, People's Republic of China.
authors.forename: Tingjiao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, People's Republic of China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Biochemistry and Molecular Biology, Dalian Medical University, Liaoning Provincial Core Lab of Glycobiology and Glycoengineering, Dalian, People's Republic of China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000071858:Epithelial Cell Adhesion Molecule; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000737:chemistry*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D048490:raf Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D061965:Matrix Metalloproteinase Inhibitors; D034741:RNA, Small Interfering; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D018631:ras Proteins
keywords: EpCAM; MMP-9; Ras/Raf/ERK; breast cancer; metastasis