Zyxin mediates actin fiber reorganization in epithelial-mesenchymal transition and contributes to endocardial morphogenesis.
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.
Division of Gene Therapy Science and Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Masaki
M
Mori
Hironori
H
Nakagami
Nobutaka
N
Koibuchi
Koichi
K
Miura
Yoichi
Y
Takami
Hiroshi
H
Koriyama
Hiroki
H
Hayashi
Hisataka
H
Sabe
Naoki
N
Mochizuki
Ryuichi
R
Morishita
Yasufumi
Y
Kaneda
D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004699:Endocardium / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022502:Stress Fibers / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism; D060589:Zyxin
D008667:Metalloproteins; D009687:Nuclear Proteins; D053773:Transforming Growth Factor beta1; D051879:Twist-Related Protein 1; C498285:Zyx protein, mouse; D060589:Zyxin; C067250:Twist1 protein, mouse; D049452:Green Fluorescent Proteins