Snail and Slug, key regulators of TGF-β-induced EMT, are sufficient for the induction of single-cell invasion

Naber, Hildegonda P. H.; Drabsch, Yvette; Snaar-Jagalska, B. Ewa; Dijke, Peter ten; Laar, Theo van

doi:10.1016/j.bbrc.2013.04.037

Cited by 118 publications

(98 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this study, we observed a role for HIF-1a in BAG3-regulated VEGF and MMP2 expression which was consistent with previous reports that HIF-1a promotes VEGF and MMP2 expression, enhancing angiogenesis and metastasis of HCC. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Moreover, BAG3 regulated angiogenesis of HCC cells through ERK phosphorylation, in accordance with previous studies. 12 Earlier work showed that autophagy-related genes could downregulate angiogenesis; 18,19 however, in our study, knockdown of BAG3 could downregulate the autophagy process.…”

Section: Bag3 Function In Human Hepatocellular Carcinomasupporting

confidence: 91%

“…It has been reported that slug is one of the transcriptional suppressors of E-cadherin, and downregulation of slug results in upregulation of E-cadherin. [25][26][27][28][29][30][31][32] Slug is one of the potential predictive biomarkers for identifying patients with lymph-node metastasis in colorectal cancer. 33 Moreover, BAG3 expression levels were significantly higher in HCC with portal vein-emboli and metastasis in our clinical analysis, and upregulation of slug in tissue in conjunction with an increase in BAG3 could reflect that cross-talk between BAG3 and EMT occurs in human HCC.…”

Section: Bag3 Function In Human Hepatocellular Carcinomamentioning

confidence: 99%

See 1 more Smart Citation

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

Xiao

Cheng

Tong

et al. 2014

Laboratory Investigation

View full text Add to dashboard Cite

Bcl2-associated athanogene 3 (BAG3) protein is a co-chaperone of heat-shock protein (Hsp) 70 and may regulate major physiological and pathophysiological processes. However, few reports have examined the role of BAG3 in human hepatocellular carcinoma (HCC). In this study, we show that BAG3 regulates epithelial-mesenchymal transition (EMT) and angiogenesis in HCC. BAG3 was overexpressed in HCC tissues and cell lines. BAG3 knockdown resulted in reduction in migration and invasion of HCC cells, which was linked to reversion of EMT by increasing E-cadherin expression and decreasing N-cadherin, vimentin and slug expression, as well as suppressing matrix metalloproteinase 2 (MMP-2) expression. In a xenograft tumorigenicity model, BAG3 knockdown effectively inhibited tumor growth and metastasis through reduction in CD34 and VEGF expression and reversal of the EMT pathway. In conclusion, BAG3 is associated with the invasiveness and angiogenesis in HCC, and the BAG3 gene may be a novel therapeutic approach against HCC.

show abstract

Section: Bag3 Function In Human Hepatocellular Carcinomasupporting

confidence: 91%

Section: Bag3 Function In Human Hepatocellular Carcinomamentioning

confidence: 99%

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

Xiao

Cheng

Tong

et al. 2014

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…Based on evidence that snail and twist increase cancer cell invasiveness, it has been proposed that they may also participate in basement membrane remodeling and motility, and this has fueled additional interest in their potential role as master regulators. However, this support of a master regulatory model is based on overexpression of snail and twist (Naber et al, 2013;Lee et al, 2006), and overexpression studies often have interpretation problems.…”

Section: *Author For Correspondence (Dmcclay@dukeedu)mentioning

confidence: 99%

“…In the chaotic cancer environment, the most infamous of the so-called EMT master regulators is snail (Wu and Zhou, 2010). Overexpression of snail in a cancer cell line is sufficient to induce EMT (Naber et al, 2013), yet overexpression in the embryo converts only a subpopulation of additional cells to an EMT state and not the entire embryo (Wu and McClay, 2007). These extra mesenchymal cells likely represent the precocious EMT of nonskeletogenic mesenchyme, a cell type already fated to undergo EMT later in development.…”

Section: Complexity Of Emt Regulationmentioning

confidence: 99%

Sub-circuits of a gene regulatory network control a developmental epithelial-mesenchymal transition

2014

View full text Add to dashboard Cite

Epithelial-mesenchymal transition (EMT) is a fundamental cell state change that transforms epithelial to mesenchymal cells during embryonic development, adult tissue repair and cancer metastasis. EMT includes a complex series of intermediate cell state changes including remodeling of the basement membrane, apical constriction, epithelial de-adhesion, directed motility, loss of apical-basal polarity, and acquisition of mesenchymal adhesion and polarity. Transcriptional regulatory state changes must ultimately coordinate the timing and execution of these cell biological processes. A wellcharacterized gene regulatory network (GRN) in the sea urchin embryo was used to identify the transcription factors that control five distinct cell changes during EMT. Single transcription factors were perturbed and the consequences followed with in vivo time-lapse imaging or immunostaining assays. The data show that five different sub-circuits of the GRN control five distinct cell biological activities, each part of the complex EMT process. Thirteen transcription factors (TFs) expressed specifically in pre-EMT cells were required for EMT. Three TFs highest in the GRN specified and activated EMT (alx1, ets1, tbr) and the 10 TFs downstream of those (tel, erg, hex, tgif, snail, twist, foxn2/3, dri, foxb, foxo) were also required for EMT. No single TF functioned in all five sub-circuits, indicating that there is no EMT master regulator. Instead, the resulting sub-circuit topologies suggest EMT requires multiple simultaneous regulatory mechanisms: forward cascades, parallel inputs and positive-feedback lock downs. The interconnected and overlapping nature of the sub-circuits provides one explanation for the seamless orchestration by the embryo of cell state changes leading to successful EMT.

show abstract

“…Previous studies indicated that high glucose (HG) induces a complex mixture of proinflammatory and profibrotic stimuli during peritoneal epithelial-to-mesenchymal transition (EMT) in vivo (2,3). EMT is a dynamic and complex process that may require the participation of numerous growth factors or cytokines (4). Therefore, factors that regulate EMT are attracting increasing attention as inducers of peritoneal fibrosis.…”

Section: Introductionmentioning

confidence: 99%

HSP70 inhibits high glucose-induced Smad3 activation and attenuates epithelial-to-mesenchymal transition of peritoneal mesothelial cells

Bao

Hao

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Heat shock proteins (HSPs) are molecular chaperones that were initially identified as proteins expressed following exposure of cells to environmental stress. However, the function of HSPs in epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells remains unknown. In the present study, the regulation of HSPs and their function in cell EMT, particularly in rat peritoneal mesothelial cells (RPMCs), and the surrounding glucose concentrations and the molecular mechanism involved were investigated. This study explored the effect of HSP70 on high glucose (HG)-induced EMT by overexpression and small interfering RNA (siRNA) knockdown of HSP70, as well as the underlying molecular mechanisms. It was found that HSP70 inhibits HG-induced EMT by modulating Smad expression and activation. HSP70 overexpression inhibited phosphorylation and nuclear translocation of p-Smad3 and p-Smad4, while siRNA of HSP70 enhanced HG-induced Smad3 and Smad4 phosphorylation and EMT. Furthermore, HSP70 suppressed EMT by inhibiting the generation of reactive oxygen species (ROS) induced by HG. In conclusion, HSP70 inhibits EMT of peritoneal mesothelial cells primarily by exerting domain-specific effects on Smad3 and Smad4 activation and reducing the release of ROS. HSP70 may be a novel therapeutic target for peritoneal dialysis patients with peritoneal fibrosis.

show abstract

Snail and Slug, key regulators of TGF-β-induced EMT, are sufficient for the induction of single-cell invasion

Cited by 118 publications

References 32 publications

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

Sub-circuits of a gene regulatory network control a developmental epithelial-mesenchymal transition

HSP70 inhibits high glucose-induced Smad3 activation and attenuates epithelial-to-mesenchymal transition of peritoneal mesothelial cells

Contact Info

Product

Resources

About