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

https://www.cell.com/cell/pdf/S0092-8674(06)01344-4.pdf

Wnt/beta-catenin signaling in development and disease.

https://web.stanford.edu/group/nusselab/cgi-bin/wnt/sites/default/files/reviews/Cell%202012%20Clevers.pdf

Wnt/β-catenin signaling and disease.

/pdf/2021-esc-guidelines-for-the-diagnosis-and-treatment-of-acute-4pqhe8c49t.pdf

2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure.

Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities.

To provide a stable environmental barrier, the epidermis requires an integrated network of cytoskeletal elements and cellular junctions. Nevertheless, the epidermis ranks among the body's most dynamic tissues, continually regenerating itself and responding to cutaneous insults. As keratinocytes journey from the basal compartment towards the cornified layers, they completely reorganize their adhesive junctions and cytoskeleton. These architectural components are more than just rivets and scaffolds - they are active participants in epidermal morphogenesis that regulate epidermal polarization, signalling and barrier formation.

/pdf/deconstructing-the-skin-cytoarchitectural-determinants-of-z7w8o82vwf.pdf

Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis.

Three proteins identified by quite different criteria in three different systems, the Drosophila segment polarity gene armadillo, the human desmosomal protein plakoglobin, and the Xenopus E-cadherin-associated protein beta-catenin, share amino acid sequence similarity. These findings raise questions about the relationship among the three molecules and their roles in different cell-cell adhesive junctions. We have found that antibodies against the Drosophila segment polarity gene armadillo cross react with a conserved vertebrate protein. This protein is membrane associated, probably via its interaction with a cadherin-like molecule. This cross-reacting protein is the cadherin-associated protein beta-catenin. Using anti-armadillo and antiplakoglobin antibodies, it was shown that beta-catenin and plakoglobin are distinct molecules, which can coexist in the same cell type. Plakoglobin interacts with the desmosomal glycoprotein desmoglein I, and weakly with E-cadherin. Although beta-catenin interacts tightly with E-cadherin, it does not seem to be associated with either desmoglein I or with isolated desmosomes. Anti-armadillo antibodies have been further used to determine the intracellular localization of beta-catenin, and to examine its tissue distribution. The implications of these results for the structure and function of different cell-cell adhesive junctions are discussed.

/pdf/the-vertebrate-adhesive-junction-proteins-beta-catenin-and-2yenkvc4mw.pdf

The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties.

https://www.jidonline.org/article/S0022-202X(15)33164-X/pdf

Desmosomes: new perspectives on a classic

Desmosomes are intercellular adhesive junctions that anchor intermediate filaments at membrane-associated plaques in adjoining cells, thereby forming a three-dimensional supracellular scaffolding that provides tissues with mechanical strength. But desmosomes have also recently been recognized as sensors that respond to environmental and cellular cues by modulating their assembly state and, possibly, their signalling functions.

Are desmosomes more than tethers for intermediate filaments

Desmosomes and hemidesmosomes are the major cell surface attachment sites for intermediate filaments at cell-cell and cell-substrate contacts, respectively. The transmembrane molecules of the desmosome belong to the cadherin family of calcium-dependent adhesion molecules, whereas those in the hemidesmosome include the integrin class of cell matrix receptors. In each junction, the cytoplasmic domains of certain transmembrane junction components contain unusually long carboxy-terminal tails not found in those family members involved in linkage of actin to the cell surface. These domains are thought to be important for the regulation of junction assembly and specific attachment of intermediate filaments via associated adapter proteins. Recent developments have suggested the exciting possibility that these junctions, in addition to playing an important structural function in tissue integrity, are both acceptors and affectors of cell signaling pathways. Many desmosomal and hemidesmosomal constituents are phosphoproteins and in certain cases the function of specific phosphorylation sites in regulating protein-protein interactions is being uncovered. In addition, a more active role in transmitting signals that control morphogenesis during development and possibly even regulate cell growth and differentiation are being defined for cytoplasmic and membrane components of these junctions.

https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fasebj.10.8.8666164

Kathleen J. Green

Papers

Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis.

The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties.

Desmosomes: new perspectives on a classic

Are desmosomes more than tethers for intermediate filaments

Desmosomes and hemidesmosomes: structure and function of molecular components.