Oncogenic roles of EMT-inducing transcription factors

Puisieux, Alain; Brabletz, Thomas; Caramel, Julie

doi:10.1038/ncb2976

Cited by 882 publications

(773 citation statements)

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“…The expression of a set of previously described epithelial to mesenchymal transition-related genes 8 was evaluated in both types of endometrial cancer clones and we found that some epithelial to mesenchymal transition genes were expressed more strongly in Ishikawa-TAZ cells, such as SNAI1 (Po0.001), SNAI2 (Po0.001), and HMGA2 (Po0.05: Figure 3a). By contrast, when TAZ expression was silenced in AN3CA cells by either of the shRNAs, we observed a decrease in the expression of the membrane factor SPARC (Po0.001), SNAI1 (Po0.01), ZEB1 (Po0.001), TCF3 (Po0.01), and HMGA2 (Po0.01: Figure 3b).…”

Section: Taz Expression Is Associated With Epithelial To Mesenchymal mentioning

confidence: 90%

“…7 The epithelial to mesenchymal transition is coordinated by a network of transcription factors that regulate the expression of proteins involved in cell polarity, cell-cell contacts, cytoskeletal structure, and extracellular matrix degradation. 8 The loss of E-cadherin expression is a crucial event in epithelial to mesenchymal transition and indeed, transcription factors associated to epithelial to mesenchymal transition can be grouped according to their ability to directly or indirectly repress E-cadherin. 9 Among the direct repressors, we can find zinc finger proteins like SNAIL1, SNAIL2, ZEB1 (TCF8), ZEB2 (SIP1), and the bHLH factor E47 (TCF3) or KLF8.…”

mentioning

confidence: 99%

“…By contrast, indirect repressors include TWIST bHLH proteins or E22. 8 In addition, the epithelial to mesenchymal transition program is closely linked to the acquisition of stem cell properties in other tumor cells, as defined by the acquisition of the CD44 high /CD24 low phenotype, in vitro self-renewal and in vivo tumor initiation capacities. 7,10 The epithelial to mesenchymal transition has also been implicated in the dissemination of primary tumors owing to invasion or intravasation, as well as to the generation of distant tumors by migrating cancer stem cells.…”

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confidence: 99%

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A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer

et al. 2015

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Although TAZ, the final effector of the Hippo pathway that modulates epithelial to mesenchymal transition and stemness, has been implicated in the development of different types of cancer, its role in endometrial cancer has not yet been studied. Thus, we evaluated the expression of TAZ in different types of endometrial cancer by immunohistochemistry. TAZ expression was detected in 76% of undifferentiated endometrial carcinomas, 54% of endometrial carcinosarcomas, 46% of endometrial serous carcinomas, 36% of grade 3 endometrioid carcinomas, and 18% of grade 1-2 endometrioid carcinomas, with statistically significant differences. We analyzed the WWTR1 gene that encodes TAZ by FISH and MassARRAY spectrometry, ruling out gene amplification and differential promoter methylation as the main mechanisms that modulate TAZ expression in endometrial tumors. However, we did detect a significant association between Scribble hypoexpression and delocalization with TAZ expression. Moreover, we demonstrated that TAZ promoted invasiveness, and it favored cell motility and tumor growth, in endometrial cancer cell lines. In addition, TAZ expression was associated with the transition from an epithelial to mesenchymal phenotype, both in vitro and in human tumors. Together, these data reveal a previously unknown role for TAZ and the Hippo pathway in the progression of aggressive subtypes of endometrial cancer. Modern Pathology (2015Pathology ( ) 28, 1492Pathology ( -1503 doi:10.1038/modpathol.2015 published online 18 September 2015 In developed countries, endometrial carcinoma is the most common malignant tumor of the female genital tract. 1 On the basis of epidemiological, clinical, pathological, and molecular features, endometrial carcinoma can be classified into at least two main categories: 2 type I estrogen-dependent carcinomas that account for 80-85% of cases and that are typically represented by low-grade (grade 1 and 2) endometrioid carcinomas, and type II endometrial carcinomas that are not estrogen dependent and that are mainly represented by a serous subtype but also by other high-grade histological tumors like clear cell or undifferentiated carcinomas. 2 In endometrial carcinoma, the epithelial to mesenchymal transition has been associated with high-grade and aggressive features. [3][4][5][6] Epithelial to

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Section: Taz Expression Is Associated With Epithelial To Mesenchymal mentioning

confidence: 90%

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confidence: 99%

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confidence: 99%

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A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer

et al. 2015

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“…5c). Since EMT is a critical process in cell migration and invasion [23,24], we further analyzed the role of GKN1 and RhoA in the expression of EMT-related proteins. In MKN1 gastric cancer cells, ectopic GKN1 expression, or silencing of RhoA, increased E-cadherin expression, and decreased the expression of RhoA, Snail, Slug, and vimentin (Fig.…”

Section: The Effects Of Gkn1 and Rhoa On Gastric Cancer Cell Migratiomentioning

confidence: 99%

Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression

et al. 2016

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Background We investigated whether GKN1, a gastric tumor suppressor, contributes to the progression of gastric cancer by regulating RhoA expression. Methods We analyzed the expression of GKN1, RhoA, miR-185, and miR-34a in 35 gastric cancer tissues, and compared their expression with T category and TNM stage. Cell migration and invasion, as well as the expression of epithelial-to-mesenchymal transition (EMT)-related proteins, were assessed in GKN1-and RhoA small interfering RNA (siRhoA)-transfected and recombinant-GKN1-treated AGS and MKN1 gastric cancer cells. Results Expression of RhoA protein and messenger RNA (mRNA) was increased in 15 (42.9 %) and 17 (48.6 %) of 35 gastric cancer tissues respectively, and was associated with higher T category and TNM stage. GKN1 expression was significantly decreased in 27 gastric cancers (77.1 %) with a higher T category, and was inversely correlated with RhoA mRNA expression. In AGS and MKN1 cells, GKN1 expression increased miR-185 and miR-34a expression and reduced RhoA mRNA and protein expression. A positive relationship between GKN1 and miR-34a and miR-185 expression and an inverse relationship between miR-34a and RhoA expression were observed in gastric cancer tissues. Cell migration and invasiveness were markedly decreased in GKN1-and siRhoA-transfected cells. GKN1 expression and silencing of RhoA decreased the expression of the proteins Snail, Slug, and vimentin. Furthermore, miR-185 and miR-34a silencing in MKN1 cells transfected with GKN1 stimulated cell migration and invasion, and increased the expression of EMT-related proteins. Conclusion Our data suggest that GKN1 may inhibit gastric cancer cell migration and invasion by downregulating RhoA expression in a miR-185-and miR-34a-dependent manner.

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“…16,17 Additional genes including WNT5, NOTCH1, CAV1 and CCND1 have also been observed in several models of EMT and metastasis. 4,[18][19][20][21] These observations indicate that H2A.X loss leads to the activation of EMT program in breast cells. As many of the movement-associated genes observed in MCF10A cells were also found to regulate EMT, migration and invasion in human colon cancer cell line HCT116, 12 our data suggest the existence of H2A.X-driven EMT signature shared by breast and colon cancer cells.…”

Section: Differential Gene Expression Analysismentioning

confidence: 74%

Twist1 and Slug mediate H2AX-regulated epithelial-mesenchymal transition in breast cells

et al. 2016

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The epithelial-mesenchymal transition (EMT) is thought to be essential for cancer metastasis. While chromatin remodeling is involved in EMT, which processes contribute to this remodeling remain poorly investigated. Recently, we showed that silencing or removal of the histone variant H2A.X induced mesenchymal-like characteristics, including activation of the EMT transcription factors, Slug and Zeb1 in human colon cancer cells. Here, we provide the evidence that H2A.X loss in human non-tumorigenic breast cell line MCF10A results in a robust EMT activation, as substantiated by a genome-wide expression analysis. Cells deficient for H2A.X exhibit enhanced migration and invasion, along with an activation of a set of mesenchymal genes and a concomitant repression of epithelial genes. In the breast model, the EMT-related transcription factor Twist1 cooperates with Slug to regulate EMT upon H2A.X Loss. Of interest, H2A.X expression level tightly correlates with Twist1, and to a lesser extent with Slug in the panel of human breast cancer cell lines of the NCI-60 datasets. These new findings indicate that H2A.X is involved in the EMT processes in cells of different origins but pairing with transcription factors for EMT may be tissue specific.

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Oncogenic roles of EMT-inducing transcription factors

Cited by 882 publications

References 135 publications

A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer

A role for the transducer of the Hippo pathway, TAZ, in the development of aggressive types of endometrial cancer

Gastrokine 1 inhibits gastric cancer cell migration and invasion by downregulating RhoA expression

Twist1 and Slug mediate H2AX-regulated epithelial-mesenchymal transition in breast cells

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