https://www.um.es/biomybiotec/web/Seminarios/2010/papers/Cano_2.pdf

Epithelial-Mesenchymal Transitions in Development and Disease

The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.

/pdf/the-basics-of-epithelial-mesenchymal-transition-xe9crzoewf.pdf

The basics of epithelial-mesenchymal transition

The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells

Without epithelial–mesenchymal transitions, in which polarized epithelial cells are converted into motile cells, multicellular organisms would be incapable of getting past the blastula stage of embryonic development. However, this important developmental programme has a more sinister role in tumour progression. Epithelial–mesenchymal transition provides a new basis for understanding the progression of carcinoma towards dedifferentiated and more malignant states.

Epithelial–mesenchymal transitions in tumour progression

The transdifferentiation of epithelial cells into motile mesenchymal cells, a process known as epithelial-mesenchymal transition (EMT), is integral in development, wound healing and stem cell behaviour, and contributes pathologically to fibrosis and cancer progression. This switch in cell differentiation and behaviour is mediated by key transcription factors, including SNAIL, zinc-finger E-box-binding (ZEB) and basic helix-loop-helix transcription factors, the functions of which are finely regulated at the transcriptional, translational and post-translational levels. The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues. Among these, transforming growth factor-β (TGFβ) family signalling has a predominant role; however, the convergence of signalling pathways is essential for EMT.

Molecular mechanisms of epithelial–mesenchymal transition

The Snail family of transcription factors has previously been implicated in the differentiation of epithelial cells into mesenchymal cells (epithelial-mesenchymal transitions) during embryonic development. Epithelial-mesenchymal transitions are also determinants of the progression of carcinomas, occurring concomitantly with the cellular acquisition of migratory properties following downregulation of expression of the adhesion protein E-cadherin. Here we show that mouse Snail is a strong repressor of transcription of the E-cadherin gene. Epithelial cells that ectopically express Snail adopt a fibroblastoid phenotype and acquire tumorigenic and invasive properties. Endogenous Snail protein is present in invasive mouse and human carcinoma cell lines and tumours in which E-cadherin expression has been lost. Therefore, the same molecules are used to trigger epithelial-mesenchymal transitions during embryonic development and in tumour progression. Snail may thus be considered as a marker for malignancy, opening up new avenues for the design of specific anti-invasive drugs.

The transcription factor Snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression

Snail is a zinc finger transcription factor that triggers the epithelial-mesenchymal transition (EMT) by directly repressing E-cadherin expression. Snail is required for mesoderm and neural crest formation during embryonic development and has recently been implicated in the EMT associated with tumour progression. In a series of human breast carcinomas, we have analysed the expression of Snail and that of molecules of the E-cadherin/catenin complexes. We have also correlated these data with the pathological features of the tumours. We show that Snail expression inversely correlates with the grade of differentiation of the tumours and that it is expressed in all the infiltrating ductal carcinomas (IDC) presenting lymph node metastases that were analysed. In addition, Snail is expressed in some dedifferentiated tumours with a negative nodal status. Considering that Snail is involved in the induction of the invasive and migratory phenotype in epithelial cells, these results indicate that it is also involved in the progression of breast ductal tumours, where it could additionally serve as a marker of the metastatic potential.

Correlation of Snail expression with histological grade and lymph node status in breast carcinomas.

The P-wave velocity structure of the mantle below the Iberian Peninsula: evidence for subducted lithosphere below southern Spain

EVC is a novel protein mutated in the human chondroectodermal dysplasia
Ellis-van Creveld syndrome (EvC; OMIM: 225500). We have inactivated
 Evc in the mouse and show that Evc -/- mice
develop an EvC-like syndrome, including short ribs, short limbs and dental
abnormalities. lacZ driven by the Evc promoter revealed that
 Evc is expressed in the developing bones and the orofacial region.
Antibodies developed against Evc locate the protein at the base of the primary
cilium. The growth plate of Evc -/- mice shows delayed bone
collar formation and advanced maturation of chondrocytes. Indian hedgehog
( Ihh ) is expressed normally in the growth plates of
 Evc -/- mice, but expression of the Ihh downstream genes
 Ptch1 and Gli1 was markedly decreased. Recent studies have
shown that Smo localises to primary cilia and that Gli3 processing is
defective in intraflagellar transport mutants. In vitro studies using
 Evc -/- cells demonstrate that the defect lies downstream
of Smo. Chondrocyte cilia are present in Evc -/- mice and
Gli3 processing appears normal by western blot analysis. We conclude that Evc
is an intracellular component of the hedgehog signal transduction pathway that
is required for normal transcriptional activation of Ihh target
genes.

/pdf/evc-is-a-positive-mediator-of-ihh-regulated-bone-growth-that-28mg4rsscb.pdf

Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia.

Present production of wild fish resources is around 85 million tonnes per year, and the maximum long-term potential of marine capture fisheries of some areas and fisheries has been reached. However, not all that is obtained from the sea is adequately used and three clearly differentiated factors can be taken into account to explain this fact: discards, wastage on board and byproducts and wastage ashore. Although some efforts have been made to change this situation, a more efficient and intelligent use is needed of the natural resources extracted from sea and wasted. In this article, the present utilization of discards and fishery wastage and also the future trends and the expected future of fishery industry are presented.

/pdf/towards-sustainable-and-efficient-use-of-fishery-resources-5wlpcg3lch.pdf

Maria Blanco

Papers

The transcription factor Snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression

Correlation of Snail expression with histological grade and lymph node status in breast carcinomas.

The P-wave velocity structure of the mantle below the Iberian Peninsula: evidence for subducted lithosphere below southern Spain

Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia.

Towards sustainable and efficient use of fishery resources: present and future trends