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PMID: 19439447 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Zyxin mediates actin fiber reorganization in epithelial-mesenchymal transition and contributes to endocardial morphogenesis.

Molecular biology of the cell ·Vol. 20 ·No. 13 ·2009-07-00 ·Pages 3115-24

Mori M, Nakagami H, Koibuchi N, Miura K, Takami Y, Koriyama H, Hayashi H, Sabe H, Mochizuki N, Morishita R, Kaneda Y

Abstract

Epithelial-mesenchymal transition (EMT) confers destabilization of cell-cell adhesion and cell motility required for morphogenesis or cancer metastasis. Here we report that zyxin, a focal adhesion-associated LIM protein, is essential for actin reorganization for cell migration in TGF-beta1-induced EMT in normal murine mammary gland (NMuMG) cells. TGF-beta1 induced the relocation of zyxin from focal adhesions to actin fibers. In addition, TGF-beta1 up-regulated zyxin via a transcription factor, Twist1. Depletion of either zyxin or Twist1 abrogated the TGF-beta1-dependent EMT, including enhanced cell motility and actin reorganization, indicating the TGF-beta1-Twist1-zyxin signal for EMT. Both zyxin and Twist1 were predominantly expressed in the cardiac atrioventricular canal (AVC) that undergoes EMT during heart development. We further performed ex vivo AVC explant assay and revealed that zyxin was required for the reorganization of actin fibers and migration of the endocardial cells. Thus, zyxin reorganizes actin fibers and enhances cell motility in response to TGF-beta1, thereby regulating EMT.

MeSH Terms
Animals Atrioventricular Node/drug effects,embryology,metabolism Blotting, Western Cell Line Cell Movement/drug effects Endocardium/drug effects,embryology,metabolism Epithelial Cells/cytology,drug effects,metabolism Focal Adhesions/drug effects,metabolism Gene Expression/drug effects Green Fluorescent Proteins/genetics,metabolism In Situ Hybridization Mesoderm/cytology,drug effects,metabolism Metalloproteins/genetics,metabolism Mice Mice, Inbred C57BL Microscopy, Confocal Morphogenesis Nuclear Proteins/genetics,metabolism RNA Interference Reverse Transcriptase Polymerase Chain Reaction Stress Fibers/metabolism Transforming Growth Factor beta1/pharmacology Twist-Related Protein 1/genetics,metabolism Zyxin
Chemicals
Metalloproteins Nuclear Proteins Transforming Growth Factor beta1 Twist-Related Protein 1 Zyx protein, mouse Zyxin Twist1 protein, mouse Green Fluorescent Proteins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Mori Masaki
Division of Gene Therapy Science and Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Nakagami Hironori
Koibuchi Nobutaka
Miura Koichi
Takami Yoichi
Koriyama Hiroshi
Hayashi Hiroki
Sabe Hisataka
Mochizuki Naoki
Morishita Ryuichi
Kaneda Yasufumi
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.e09-01-0046
Published
2009-07-00
Epub
2009-00-13
Pages
3115-24
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2704162
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e09-01-0046 PMC Full Text View journal details
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