title: Fascin, an actin-bundling protein, promotes breast cancer progression in vitro.
abstract: Fascin, an actin-cross-linking protein, is up-regulated in breast cancer and correlates with a more aggressive disease. This study was conducted to elucidate the effects of manipulating fascin in breast cancer cells on the metastasis-associated events, including proliferation, adhesion, invasion, epithelial-mesenchymal transition (EMT) and enrichment of a CD44(+) /CD24(-) subpopulation that show some stem/progenitor cell properties. Western blot analysis of a panel of breast cancer cell lines revealed high expression of fascin in MDA-MB-435 and MDA-MB-231 cells but revealed no or low expression in MDA-MB-453, Her-18 and T47D. Gain-of-function and loss-of-function studies in breast cancer cells demonstrated that forced expression of fascin promoted cell proliferation assessed by the MTT assay, decreased cellular adhesion to fibronectin and potentiated the invasive capacity in the Transwell chamber invasion assay. Conversely, down-regulation of fascin via small interfering RNA increased cell adhesion and facilitated cell proliferation and invasion. In addition, fascin participated in the EMT and modulated the proportion of the CD44(+) /CD24(-) subpopulation in breast cancer cells. In conclusion, our data highlight an important role for fascin in breast cancer progression in vitro through orchestrating a variety of cellular events associated with metastasis, and thus, targeting this gene might have therapeutic implications.
authors.affiliation: Breast Surgery, Department of Surgical Oncology, General Surgery, First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xing
authors.forename: Ji-guang
authors.initials: JG
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Zhao
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
authors.forename: Hui-ting
authors.initials: HT
authors.lastname: Dong
authors.forename: Xiao-lin
authors.initials: XL
authors.lastname: Wei
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D051927:CD24 Antigen / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; C020324:fascin