Expression of the Transcription Factors Snail, Slug, and Twist and Their Clinical Significance in Human Breast Cancer

Martin, Tracey Amanda; Goyal, Amit; Watkins, Gareth; Jiang, Wen Guo

doi:10.1245/aso.2005.04.010

Cited by 430 publications

(341 citation statements)

References 35 publications

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“…Nevertheless, the dorsoanterior development, craniofacial patterning, and marker expression in the embryos and of the resulting larvae were normal, revealing that this effect is not inducing major alterations of head or heart morphogenesis (as would be expected if large numbers of cells were diverted from other neural crest lineages or if major and nonspecific changes in signaling factor expression were being caused). These data reveal that KCNE1 misexpression induces ectopic expression of powerful regulators of both neural crest and neoplastic cell behavior (35)(36)(37)(38).…”

Section: Kcne1 Induces Neural Crest/tumor Regulator Gene Expression In Amentioning

confidence: 87%

Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells

Morokuma¹,

Blackiston²,

Adams³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

102

124

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Ion transporters, and the resulting voltage gradients and electric fields, have been implicated in embryonic development and regeneration. These biophysical signals are key physiological aspects of the microenvironment that epigenetically regulate stem and tumor cell behavior. Here, we identify a previously unrecognized function for KCNQ1, a potassium channel known to be involved in human Romano-Ward and Jervell-Lange-Nielsen syndromes when mutated. Misexpression of its modulatory wild-type ␤-subunit XKCNE1 in the Xenopus embryo resulted in a striking alteration of the behavior of one type of embryonic stem cell: the pigment cell lineage of the neural crest. Depolarization of embryonic cells by misexpression of KCNE1 non-cell-autonomously induced melanocytes to overproliferate, spread out, and become highly invasive of blood vessels, liver, gut, and neural tube, leading to a deeply hyperpigmented phenotype. This effect is mediated by the up-regulation of Sox10 and Slug genes, thus linking alterations in ion channel function to the control of migration, shape, and mitosis rates during embryonic morphogenesis. Taken together, these data identify a role for the KCNQ1 channel in regulating key cell behaviors and reveal the molecular identity of a biophysical switch, by means of which neoplastic-like properties can be conferred upon a specific embryonic stem cell subpopulation.cancer ͉ ion channel ͉ melanocyte ͉ neural crest ͉ KCNQ

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Section: Kcne1 Induces Neural Crest/tumor Regulator Gene Expression In Amentioning

confidence: 87%

Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells

Morokuma¹,

Blackiston²,

Adams³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

102

124

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show abstract

“…The tumor invasion and metastasis are initiated by EMT program involving cells acquiring mesenchymal phenotype characterized with decreased cell‐to‐cell adhesion, increased motility and invasive properties. Such cells once detached from primary tumor invade surrounding tissues through collective or individual cell migration 3, 20, 21, 22, 23, 24, 25, 26, 67, 68, 69, 70, 71, 73. Therefore, we propose that fibroblasts infected with H. pylori (cagA+vacA+) likely acquired characteristics of CAFs with changes in morphology and elevated HGF, TGFβ, and additionally IL‐6 and SDF‐1 release, which may enhance EMT program in epithelial gastric cells.…”

Section: Discussionmentioning

confidence: 99%

“…These events are facilitated by the reduction in cell‐cell adhesion molecule E‐cadherin, the upregulation of more plastic mesenchymal proteins such as vimentin, N‐cadherin, and α‐SMA and deregulation of the Wnt pathway 23, 24. Many EMT‐inducing transcription factors (EMT‐TFs) such as Twist1, Snail1, Snail2, Zeb1, and Zeb2 can repress E‐cadherin both directly or indirectly 23, 24, 25, 26…”

Section: Introductionmentioning

confidence: 99%

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

et al. 2018

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BackgroundMajor human gastrointestinal pathogen Helicobacter pylori (H. pylori) colonizes the gastric mucosa causing inflammation and severe complications including cancer, but the involvement of fibroblasts in the pathogenesis of these disorders in H. pylori‐infected stomach has been little studied. Normal stroma contains few fibroblasts, especially myofibroblasts. Their number rapidly increases in the reactive stroma surrounding inflammatory region and neoplastic tissue; however, the interaction between H. pylori and fibroblasts remains unknown. We determined the effect of coincubation of normal rat gastric fibroblasts with alive H. pylori (cagA+vacA+) and H. pylori (cagA−vacA−) strains on the differentiation of these fibroblasts into cells possessing characteristics of cancer‐associated fibroblasts (CAFs) able to induce epithelial‐mesenchymal transition (EMT) of normal rat gastric epithelial cells (RGM‐1).Materials and MethodsThe panel of CAFs markers mRNA was analyzed in H. pylori (cagA+vacA+)‐infected fibroblasts by RT‐PCR. After insert coculture of differentiated fibroblasts with RGM‐1 cells from 24 up to 48, 72, and 96 hours, the mRNA expression for EMT‐associated genes was analyzed by RT‐PCR.ResultsThe mRNA expression for CAFs markers was significantly increased after 72 hours of infection with H. pylori (cagA+vacA+) but not H. pylori (cagA−vacA−) strain. Following coculture with CAFs, RGM‐1 cells showed significant decrease in E‐cadherin mRNA, and the parallel increase in the expression of Twist and Snail transcription factors mRNA was observed along with the overexpression of mRNAs for TGFβR, HGFR, FGFR, N‐cadherin, vimentin, α‐SMA, VEGF, and integrin‐β1.Conclusion Helicobacter pylori (cagA+vacA+) strain induces differentiation of normal fibroblasts into CAFs, likely to initiate the EMT process in RGM‐1 epithelial cell line.

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“…Snail can down-regulate expression of E-cadherin, inducing EMT and promoting cell migration and invasion [22,44] . Overexpression of Snail was detected in various tumor cell lines, including breast, pancreatic and gastric cancers [45][46][47] . It was recently reported that Akt could up-regulate Snail expression and induce invasion [40,48] .…”

Section: Discussionmentioning

confidence: 99%

Gambogic acid inhibits TNF-α-induced invasion of human prostate cancer PC3 cells in vitro through PI3K/Akt and NF-κB signaling pathways

et al. 2012

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Aim: To investigate the mechanisms underlying the inhibitory effect of gambogic acid (GA) on TNF-α-induced metastasis of human prostate cancer PC3 cells in vitro. Methods: TNF-α-mediated migration and invasion of PC3 cells was examined using migration and invasion assays, respectively. NF-κB transcriptional activity and nuclear translocation were analyzed with luciferase reporter gene assays, immunofluorescence assays and Western blots. The ability of p65 to bind the promoter of Snail, an important mesenchymal molecular marker, was detected using a chromatin immunoprecipitation (ChIP) assay. After treatment with Snail-specific siRNA, the expression of invasiveness-associated genes was measured using quantitative real-time PCR and Western blot. Results: GA significantly inhibited the viability of PC3 cells at 1-5 μmol/L, but did not produce cytotoxic effect at the concentrations below 0.5 μmol/L. GA (0.125-0.5 μmol/L) dose-dependently inhibited the migration and invasion of PC3 cells induced by TNF-α (10 ng/mL). Moreover, the TNF-α-mediated activation of phosphatidylinositol-3-OH kinase/protein kinase B (PI3K/Akt) and NF-κB pathways was suppressed by GA (0.5 μmol/L). Furthermore, this anti-invasion effect of GA was associated with regulation of Snail. Snail expression was significantly down-regulated by treatment with GA (0.5 μmol/L) in the TNF-α-stimulated PC3 cells. Conclusion: GA inhibits TNF-α-induced invasion of PC3 cells via inactivation of the PI3K/Akt and NF-κB signaling pathways, which may offer a novel approach for the treatment of human prostate cancer.

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Expression of the Transcription Factors Snail, Slug, and Twist and Their Clinical Significance in Human Breast Cancer

Abstract: These data demonstrate that all three transcription factors have inappropriate expression in breast cancer and that this may play a part in the progression of human breast tumors.

Cited by 430 publications

References 35 publications

Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells

Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

Gambogic acid inhibits TNF-α-induced invasion of human prostate cancer PC3 cells in vitro through PI3K/Akt and NF-κB signaling pathways

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