<i>N-cadherin</i> Gene Expression in Prostate Carcinoma Is Modulated by Integrin-Dependent Nuclear Translocation of Twist1

Alexander, Nelson R.; Tran, Nhan L.; Rekapally, Harish; Summers, Carol E.; Glackin, Carlotta A.; Heimark, Ronald L.

doi:10.1158/0008-5472.can-05-3401

Cited by 225 publications

(165 citation statements)

References 19 publications

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“…Consistent with its activation of E-cadherin expression, ATRA inhibited BLM-induced Snail and Twist expression, further supporting that ATRA ameliorated lung fibrosis via inhibiting EMT. Recent studies 40,43,[45][46][47] support our findings. For example, Snail and Twist are upregulated by the majority of EMT inducers and they play a crucial role in this transforming event.…”

Section: Discussionsupporting

confidence: 90%

All-transretinoic acid ameliorates bleomycin-induced lung fibrosis by downregulating the TGF-β1/Smad3 signaling pathway in rats

Song

Liu

Xie

et al. 2013

Laboratory Investigation

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Section: Discussionsupporting

confidence: 90%

All-transretinoic acid ameliorates bleomycin-induced lung fibrosis by downregulating the TGF-β1/Smad3 signaling pathway in rats

Song

Liu

Xie

et al. 2013

Laboratory Investigation

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“…Twist1 is an established repressor of E-cadherin gene transcription during EMT, 14,15 and it directly induces N-cadherin expression in PC cells. 16 Moreover, Twist1 has been shown to induce RAC1 activity 22 and formation of invadopodia in cancer cells. 24 The regulatory regions of the Twist1 gene contain the g-interferoneactivated sequence, 85 a binding element shared by Stat3 and Stat5a/ b, and Stat3 has been shown to up-regulate Twist1 gene expression in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Jak2-Stat5a/b Signaling Induces Epithelial-to-Mesenchymal Transition and Stem-Like Cell Properties in Prostate Cancer

Talati

Ellsworth

et al. 2015

The American Journal of Pathology

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Active Stat5a/b predicts early recurrence and disease-specific death in prostate cancer (PC), which both typically are caused by development of metastatic disease. Herein, we demonstrate that Stat5a/b induces epithelial-to-mesenchymal transition (EMT) of PC cells, as shown by Stat5a/b regulation of EMT marker expression (Twist1, E-cadherin, N-cadherin, vimentin, and fibronectin) in PC cell lines, xenograft tumors in vivo, and patient-derived PCs ex vivo using organ explant cultures. Jak2-Stat5a/b signaling induced functional end points of EMT as well, indicated by disruption of epithelial cell monolayers and increased migration and adhesion of PC cells to fibronectin. Knockdown of Twist1 suppressed Jak2-Stat5a/beinduced EMT properties of PC cells, which were rescued by re-introduction of Twist1, indicating that Twist1 mediates Stat5a/b-induced EMT in PC cells. While promoting EMT, Jak2-Stat5a/b signaling induced stemlike properties in PC cells, such as sphere formation and expression of cancer stem cell markers, including BMI1. Mechanistically, both Twist1 and BMI1 were critical for Stat5a/b induction of stem-like features, because genetic knockdown of Twist1 suppressed Stat5a/b-induced BMI1 expression and sphere formation in stem cell culture conditions, which were rescued by re-introduction of BMI1. By using human prolactin knock-in mice, we demonstrate that prolactin-Stat5a/b signaling promoted metastases formation of PC cells in vivo. In conclusion, our data support the concept that Jak2-Stat5a/b signaling promotes metastatic progression of PC by inducing EMT and stem cell properties in PC cells. Most prostate cancer (PC)erelated deaths are because of development of metastatic disease. A central process in metastatic dissemination of PC is epithelial-to-mesenchymal transition (EMT), during which cancer cells attain more motile and invasive properties, invade through the basement membrane, and survive in systemic circulation. 1e3 Extravasation at distant organ sites is followed by adhesion of cancer cells to extracellular matrix proteins, such as fibronectin, 4e6 leading to formation of premetastatic niches and subsequent formation of macroscopic metastases. 7e9 Hallmarks of EMT in PC include disruption of adherens junctions through down-regulation of E-cadherin, 2 concomitant with a development of a migratory phenotype and up-regulation of mesenchymal markers, such as N-cadherin, vimentin, and fibronectin. 10,11 Loss of E-cadherin results from mutations, DNA methylation, or silencing of E-cadherin promoter

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“…2 c). On the transcriptional level, the transcriptional repressor Twist appears to be involved in the induction of N-cadherin gene expression in an β 1 -integrin-dependent manner [78][79][80]. Like its epithelial counterpart, N-cadherin is connected via α-catenin and β-catenin to the cytoskeleton and functions as both a mechanical cell adhesion component and a signaling molecule.…”

Section: The Cadherin Switch and Its Consequencesmentioning

confidence: 99%

EMT, the cytoskeleton, and cancer cell invasion

Yilmaz

Christofori

2009

Cancer Metastasis Rev

1,528

1,314

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The metastatic process, i.e. the dissemination of cancer cells throughout the body to seed secondary tumors at distant sites, requires cancer cells to leave the primary tumor and to acquire migratory and invasive capabilities. In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. The molecular processes underlying such cellular changes are still only poorly understood, and the various migratory organelles, including lamellipodia, filopodia, invadopodia and podosomes, still require a better functional and molecular characterization. Notably, direct experimental evidence linking the formation of migratory membrane protrusions and the process of EMT and tumor metastasis is still lacking. In this review, we have summarized recent novel insights into the molecular processes and players underlying EMT on one side and the formation of invasive membrane protrusions on the other side.

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N-cadherin Gene Expression in Prostate Carcinoma Is Modulated by Integrin-Dependent Nuclear Translocation of Twist1

Cited by 225 publications

References 19 publications

All-transretinoic acid ameliorates bleomycin-induced lung fibrosis by downregulating the TGF-β1/Smad3 signaling pathway in rats

All-transretinoic acid ameliorates bleomycin-induced lung fibrosis by downregulating the TGF-β1/Smad3 signaling pathway in rats

Jak2-Stat5a/b Signaling Induces Epithelial-to-Mesenchymal Transition and Stem-Like Cell Properties in Prostate Cancer

EMT, the cytoskeleton, and cancer cell invasion

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