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siRNA gelsolin knockdown induces epithelial‐mesenchymal transition with a cadherin switch in human mammary epithelial cells
Author(s) -
Tanaka Hiroki,
Shirkoohi Reza,
Nakagawa Koji,
Qiao Hongjiang,
Fujita Hisakazu,
Okada Futoshi,
Hamada Junichi,
Kuzumaki Satoshi,
Takimoto Masato,
Kuzumaki Noboru
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21559
Subject(s) - epithelial–mesenchymal transition , gene knockdown , microbiology and biotechnology , small interfering rna , biology , gelsolin , cadherin , motility , actin , cancer research , transfection , cell culture , cell , downregulation and upregulation , biochemistry , genetics , gene
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. © 2005 Wiley‐Liss, Inc.