siRNA gelsolin knockdown induces epithelial-mesenchymal transition with a cadherin switch in human mammary epithelial cells

Authors

  • Hiroki Tanaka,

    1. Division of Cancer Gene Regulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
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    • The first 2 authors contributed equally to this work.

  • Reza Shirkoohi,

    1. Division of Cancer Gene Regulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
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    • The first 2 authors contributed equally to this work.

  • Koji Nakagawa,

    1. Division of Cancer Gene Regulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
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  • Hongjiang Qiao,

    1. Division of Cancer Gene Regulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
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  • Hisakazu Fujita,

    1. Department of Structural Analysis, Research Institute, National Cardiovascular Center, Osaka, Japan
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  • Futoshi Okada,

    1. Department of Biomolecular Function, Graduate School of Medical Science, Yamagata University, Yamagata, Japan
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  • Jun-ichi Hamada,

    1. Division of Cancer-Related Genes, Research Section of Molecular Pathogenesis, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
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  • Satoshi Kuzumaki,

    1. Division of Cancer Gene Regulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
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  • Masato Takimoto,

    1. Division of Cancer Gene Regulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
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  • Noboru Kuzumaki

    Corresponding author
    1. Division of Cancer Gene Regulation, Research Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
    • Division of Cancer Gene Regulation, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-Ku, Sapporo 060-0815, Japan
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    • Fax: +81-11-706-7869.


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. © 2005 Wiley-Liss, Inc.

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