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00085472can142387-sup-131463_1_supp_2712877_ndssrs.png (1.55 MB)

Supplementary Figure S1 from SND1 Acts Downstream of TGFβ1 and Upstream of Smurf1 to Promote Breast Cancer Metastasis

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posted on 2023-03-30, 23:32 authored by Lin Yu, Xin Liu, Kang Cui, Yanbo Di, Lingbiao Xin, Xiaoming Sun, Wei Zhang, Xi Yang, Minxin Wei, Zhi Yao, Jie Yang

Supplementary Figure S1. Gain-of-function of SND1 in stable SND1-knockdown cell line could reverse the phenotype induced by lacking of SND1.

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ARTICLE ABSTRACT

SND1 is an AEG-1/MTDH/LYRIC-binding protein that is upregulated in numerous human cancers, where it has been assigned multiple functional roles. In this study, we report its association with the TGFβ1 signaling pathway, which promotes epithelial–mesenchymal transition (EMT) in breast cancer. SND1 was upregulated in breast cancer tissues, in particular in primary invasive ductal carcinomas. Transcriptional activation of the SND1 gene was controlled by the TGFβ1/Smad pathway, specifically by activation of the Smad2/Smad3 complex. The SND1 promoter region contained several Smad-specific recognition domains (RD motifs), which were recognized and bound by the Smad complex that enhanced the transcriptional activation of SND1. We found that SND1 promoted expression of the E3 ubiquitin ligase Smurf1, leading to RhoA ubiquitination and degradation. RhoA degradation in breast cancer cells disrupted F-actin cytoskeletal organization, reduced cell adhesion, increased cell migration and invasion, and promoted metastasis. Overall, our results define a novel role for SND1 in regulating breast tumorigenesis and metastasis. Cancer Res; 75(7); 1275–86. ©2015 AACR.