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01-12-2013 | Research Paper

Cooperative involvement of NFAT and SnoN mediates transforming growth factor-β (TGF-β) induced EMT in metastatic breast cancer (MDA-MB 231) cells

Authors: Suman Sengupta, Samir Jana, Subir Biswas, Palash Kumar Mandal, Arindam Bhattacharyya

Published in: Clinical & Experimental Metastasis | Issue 8/2013

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-β mediated mechanism of EMT in breast cancer (MDA-MB 231) cells. Initial exposure of TGF-β 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-β 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-β mediated EMT. Silencing of NFAT also showed the inhibition of TGF-β 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-β mediated EMT by recruiting the effector molecules N-cadherin and MMP-2, MMP-9.

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Title: Cooperative involvement of NFAT and SnoN mediates transforming growth factor-β (TGF-β) induced EMT in metastatic breast cancer (MDA-MB 231) cells
Authors: Suman Sengupta
Samir Jana
Subir Biswas
Palash Kumar Mandal
Arindam Bhattacharyya
Publication date: 01-12-2013
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 8/2013
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-013-9600-y

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