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Epithelial Plasticity in Cancer: Unmasking a MicroRNA Network for TGF-β-, Notch-, and Wnt-Mediated EMT.

Zoni E, van der Pluijm G, Gray PC, Kruithof-de Julio M - J Oncol (2015)

Bottom Line: Altered microRNA (miR) expression and perturbed signalling pathways have been associated with epithelial plasticity, including oncogenic EMT.In this review we analyse and describe the interaction between experimentally validated miRs and their target genes in TGF-β, Notch, and Wnt signalling pathways.Interestingly, in this process, we identified a "signature" of 30 experimentally validated miRs and a cluster of validated target genes that seem to mediate the cross talk between TGF-β, Notch, and Wnt signalling networks during EMT and reinforce their connection to the regulation of epithelial plasticity in health and disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

ABSTRACT
Epithelial-to-mesenchymal transition (EMT) is a reversible process by which cancer cells can switch from a sessile epithelial phenotype to an invasive mesenchymal state. EMT enables tumor cells to become invasive, intravasate, survive in the circulation, extravasate, and colonize distant sites. Paracrine heterotypic stroma-derived signals as well as paracrine homotypic or autocrine signals can mediate oncogenic EMT and contribute to the acquisition of stem/progenitor cell properties, expansion of cancer stem cells, development of therapy resistance, and often lethal metastatic disease. EMT is regulated by a variety of stimuli that trigger specific intracellular signalling pathways. Altered microRNA (miR) expression and perturbed signalling pathways have been associated with epithelial plasticity, including oncogenic EMT. In this review we analyse and describe the interaction between experimentally validated miRs and their target genes in TGF-β, Notch, and Wnt signalling pathways. Interestingly, in this process, we identified a "signature" of 30 experimentally validated miRs and a cluster of validated target genes that seem to mediate the cross talk between TGF-β, Notch, and Wnt signalling networks during EMT and reinforce their connection to the regulation of epithelial plasticity in health and disease.

No MeSH data available.


Related in: MedlinePlus

Venn diagram showing number of overlapping, experimentally validated miRs targeting KEGG pathway genes from the TGF-β, Wnt, and Notch pathways.
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fig1: Venn diagram showing number of overlapping, experimentally validated miRs targeting KEGG pathway genes from the TGF-β, Wnt, and Notch pathways.

Mentions: Using TarBase v6.0 we explored the collection of manually curated, experimentally validated miR interactions with genes in the TGF-β, Wnt, and Notch KEGG pathways. We identified 84 experimentally validated miRs interacting with genes involved in the TGF-β signalling pathway, 104 miRs in the Wnt pathway, and 48 miRs interacting with genes involved in Notch signalling. We clustered the miRs identified in our search in order to obtain a list of experimentally validated miRs shared between all three pathways focusing first on clusters of two out of three pathways (i.e., experimentally validated miRs shared between only TGF-β and Notch, TGF-β and Wnt, or Notch and Wnt) (Figure 1). We identified 2 experimentally validated miRs shared between the TGF-β and Notch pathways (Figure 1 and Supplementary Table 1 available online at http://dx.doi.org/10.1155/2015/198967); 10 miRs shared between the Notch and Wnt pathways (Figure 1 and Supplementary Table 2); 39 miRs shared between the TGF-β and Wnt pathways (Figure 1 and Supplementary Table 3). We further identified a signature of 30 experimentally validated miRs targeting all three pathways (Figure 1 and Tables 1, 2, and 3). Within this 30-miR signature, 4 miRs (miR-103a, miR-132, miR-30a, and miR-10a) had validated target genes not ascribable to the manually annotated interactions within the KEGG pathways.


Epithelial Plasticity in Cancer: Unmasking a MicroRNA Network for TGF-β-, Notch-, and Wnt-Mediated EMT.

Zoni E, van der Pluijm G, Gray PC, Kruithof-de Julio M - J Oncol (2015)

Venn diagram showing number of overlapping, experimentally validated miRs targeting KEGG pathway genes from the TGF-β, Wnt, and Notch pathways.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4390187&req=5

fig1: Venn diagram showing number of overlapping, experimentally validated miRs targeting KEGG pathway genes from the TGF-β, Wnt, and Notch pathways.
Mentions: Using TarBase v6.0 we explored the collection of manually curated, experimentally validated miR interactions with genes in the TGF-β, Wnt, and Notch KEGG pathways. We identified 84 experimentally validated miRs interacting with genes involved in the TGF-β signalling pathway, 104 miRs in the Wnt pathway, and 48 miRs interacting with genes involved in Notch signalling. We clustered the miRs identified in our search in order to obtain a list of experimentally validated miRs shared between all three pathways focusing first on clusters of two out of three pathways (i.e., experimentally validated miRs shared between only TGF-β and Notch, TGF-β and Wnt, or Notch and Wnt) (Figure 1). We identified 2 experimentally validated miRs shared between the TGF-β and Notch pathways (Figure 1 and Supplementary Table 1 available online at http://dx.doi.org/10.1155/2015/198967); 10 miRs shared between the Notch and Wnt pathways (Figure 1 and Supplementary Table 2); 39 miRs shared between the TGF-β and Wnt pathways (Figure 1 and Supplementary Table 3). We further identified a signature of 30 experimentally validated miRs targeting all three pathways (Figure 1 and Tables 1, 2, and 3). Within this 30-miR signature, 4 miRs (miR-103a, miR-132, miR-30a, and miR-10a) had validated target genes not ascribable to the manually annotated interactions within the KEGG pathways.

Bottom Line: Altered microRNA (miR) expression and perturbed signalling pathways have been associated with epithelial plasticity, including oncogenic EMT.In this review we analyse and describe the interaction between experimentally validated miRs and their target genes in TGF-β, Notch, and Wnt signalling pathways.Interestingly, in this process, we identified a "signature" of 30 experimentally validated miRs and a cluster of validated target genes that seem to mediate the cross talk between TGF-β, Notch, and Wnt signalling networks during EMT and reinforce their connection to the regulation of epithelial plasticity in health and disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.

ABSTRACT
Epithelial-to-mesenchymal transition (EMT) is a reversible process by which cancer cells can switch from a sessile epithelial phenotype to an invasive mesenchymal state. EMT enables tumor cells to become invasive, intravasate, survive in the circulation, extravasate, and colonize distant sites. Paracrine heterotypic stroma-derived signals as well as paracrine homotypic or autocrine signals can mediate oncogenic EMT and contribute to the acquisition of stem/progenitor cell properties, expansion of cancer stem cells, development of therapy resistance, and often lethal metastatic disease. EMT is regulated by a variety of stimuli that trigger specific intracellular signalling pathways. Altered microRNA (miR) expression and perturbed signalling pathways have been associated with epithelial plasticity, including oncogenic EMT. In this review we analyse and describe the interaction between experimentally validated miRs and their target genes in TGF-β, Notch, and Wnt signalling pathways. Interestingly, in this process, we identified a "signature" of 30 experimentally validated miRs and a cluster of validated target genes that seem to mediate the cross talk between TGF-β, Notch, and Wnt signalling networks during EMT and reinforce their connection to the regulation of epithelial plasticity in health and disease.

No MeSH data available.


Related in: MedlinePlus