siRNA gelsolin knockdown induces epithelial-mesenchymal transition with a cadherin switch in human mammary epithelial cells.
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.
Tanaka
Hiroki
H
Division of Cancer Gene Regulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Shirkoohi
Reza
R
Nakagawa
Koji
K
Qiao
Hongjiang
H
Fujita
Hisakazu
H
Okada
Futoshi
F
Hamada
Jun-Ichi
J
Kuzumaki
Satoshi
S
Takimoto
Masato
M
Kuzumaki
Noboru
N
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
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