title: siRNA gelsolin knockdown induces epithelial-mesenchymal transition with a cadherin switch in human mammary epithelial cells.
abstract: Epithelial-mesenchymal transition (EMT) describes a process occurring during development and oncogenesis by which epithelial cells obtain fibroblast-like properties and show reduced cell adhesion and increased motility. In this report, we demonstrated typical EMT in human mammary epithelial MCF10A small interfering (si)RNA gelsolin-knockdown cells. EMT was characterized by fibroblastic morphology, loss of contact inhibition and focus formation in monolayer growth, enhanced motility and invasiveness in vitro, increased actin filaments, overexpression of RAC, activation of both extracellular signal-regulated kinase and AKT, inactivation of glycogen synthase kinase-3, conversion of cadherin from the E- to N-type and induction of the transcription factor Snail. These results suggested that gelsolin functions as a switch that controls E- and N-cadherin conversion via Snail, and demonstrated that its knockdown leads to EMT in human mammary epithelial cells and possibly to the development of human mammary tumors.
authors.affiliation: Division of Cancer Gene Regulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Reza
authors.initials: R
authors.lastname: Shirkoohi
authors.forename: Koji
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Qiao
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Fujita
authors.forename: Futoshi
authors.initials: F
authors.lastname: Okada
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Hamada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuzumaki
authors.forename: Masato
authors.initials: M
authors.lastname: Takimoto
authors.forename: Noboru
authors.initials: N
authors.lastname: Kuzumaki
mesh_terms: D001943:Breast Neoplasms / Q000503:physiopathology; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000502:physiology*; D004848:Epithelium; D005260:Female; D005347:Fibroblasts; D018260:Gelsolin / Q000096:biosynthesis*; D005812:Genes, Switch; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology* / Q000502:physiology; D008648:Mesoderm; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000502:physiology
chemical_list: D015820:Cadherins; D018260:Gelsolin; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3