Cooperative involvement of NFAT and SnoN mediates transforming growth factor-ß (TGF-ß) induced EMT in metastatic breast cancer (MDA-MB 231) cells.
Clin Exp Metastasis
; 30(8): 1019-31, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-23832742
ABSTRACT
Epithelial to mesenchymal transition (EMT) is a secondary phenomenon concomitantly associated with the tumor progression. The regulatory signals and mechanistic details of EMT are not fully elucidated. Here, we shared a TGF-ß mediated mechanism of EMT in breast cancer (MDA-MB 231) cells. Initial exposure of TGF-ß for 48 h, enhanced the rate of cell proliferation and associated with EMT of MDA-MB 231 cells. The EMT was characterized by observing the increased N-cadherin, fibronectin, Snail expression and associated with the morphological change with a reduced E-cadherin expression. NFAT, a transcription factor, alters tumor suppressive function of TGF-ß towards tumor progression. Up regulation of NFAT, coupled with a foremost translocation of one oncogenic protein SnoN from cytoplasm to nucleus was noticed during this TGF-ß mediated EMT. Silencing of NFAT also showed the inhibition of TGF-ß mediated EMT characterized by down regulation of N-cadherin and associated with reduced expression of SnoN. In addition, it was also observed that NFAT sequestering the Smad3 prevents the proteasome mediated degradation of SnoN and this SnoN has a role on the regulation of MMP-2, MMP-9 activity. Increased Smad3-SnoN interaction and proteasome mediated degradation of SnoN were detected after silencing of NFAT with a reduced MMP-2, MMP-9 activity. All of these observations provide a fresh mechanism in which by a twofold involvement of NFAT and SnoN plays a crucial role in TGF-ß mediated EMT by recruiting the effector molecules N-cadherin and MMP-2, MMP-9.
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MEDLINE
Assunto principal:
Neoplasias da Mama
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Fator de Crescimento Transformador beta
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Proteínas Proto-Oncogênicas
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Peptídeos e Proteínas de Sinalização Intracelular
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Fatores de Transcrição NFATC
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Transição Epitelial-Mesenquimal
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article