TY - JOUR
T1 - Zyxin mediates actin fiber reorganization in epithelial-mesenchymal transition and contributes to endocardial morphogenesis
AU - Mori, Masaki
AU - Nakagami, Hironori
AU - Koibuchi, Nobutaka
AU - Miura, Koichi
AU - Takami, Yoichi
AU - Koriyama, Hiroshi
AU - Hayashi, Hiroki
AU - Sabe, Hisataka
AU - Mochizuki, Naoki
AU - Morishita, Ryuichi
AU - Kaneda, Yasufumi
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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-β1-induced EMT in normal murine mammary gland (NMuMG) cells. TGF-β1 induced the relocation of zyxin from focal adhesions to actin fibers. In addition, TGF-β1 up-regulated zyxin via a transcription factor, Twist1. Depletion of either zyxin or Twist1 abrogated the TGF-β1-dependent EMT, including enhanced cell motility and actin reorganization, indicating the TGF-β1-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-β1, thereby regulating EMT.
AB - 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-β1-induced EMT in normal murine mammary gland (NMuMG) cells. TGF-β1 induced the relocation of zyxin from focal adhesions to actin fibers. In addition, TGF-β1 up-regulated zyxin via a transcription factor, Twist1. Depletion of either zyxin or Twist1 abrogated the TGF-β1-dependent EMT, including enhanced cell motility and actin reorganization, indicating the TGF-β1-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-β1, thereby regulating EMT.
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U2 - 10.1091/mbc.E09-01-0046
DO - 10.1091/mbc.E09-01-0046
M3 - Article
C2 - 19439447
AN - SCOPUS:67650427412
SN - 1059-1524
VL - 20
SP - 3115
EP - 3124
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 13
ER -
