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Epithelial Cells
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
A variety of proteins and glycoproteins make up the different portions of the desmosome. Membrane glycoproteins, known as desmogleins or desmocollins, project into the intercellular space to form an intercellular adhesive structure (45). Three desmogleins have been identified (48): desmoglein I has a molecular weight of 150 kD, desmoglein II is a 110–120 kD protein, and desmoglein III is considerably smaller (22 kD). Although desmoglein I is also found in the desmosomal plaque (49), the cytoplasmic side of the desmosome is primarily composed of four nonglycosylated proteins called desmoplakins. Desmoplakins I and II (250 kD and 215 kD, respectively) are somewhat larger proteins than desmoplakins III and IV (83 kD and 78 kD, respectively) (50). Desmin, vimentin, and particularly cytokeratin, make up the tonofilaments (45). Cytokeratin expression is often used as a characteristic feature of epithelial cells.
Pemphigus
Published in Lionel Fry, Atlas of Bullous Diseases, 2020
The primary pathological event in pemphigus is the loss of adhesion of the epidermal cells. The attachment of epidermal cells is mainly through the desmosomes, and to a lesser extent by so-called ‘tight’ or ‘adherence’ junctions. The desmosome is made up of structures called Cadherins which are divided into desmogleins and desmocollins. These structures have an intracellular, a transmembrane and an extracellular component. Intracellularly they are attached to the keratin cytoskeleton and extra-cellularly to that of another cell forming the desmosome (Figure 3.2). Desmogleins are subdivided into desmogleins 1, 2 and 3 and are intracellular components of the desmosome (Figure 3.2). Desmoglein 3 is expressed only in the basal and suprabasal layers of the epidermis, whereas desmoglein 1 is expressed throughout the epidermis but mainly in the upper layers. In mucosae, desmoglein 3 is strongly expressed throughout the epithelium and desmoglein 1 only weakly.
Arrhythmogenic Right Ventricular Cardiomyopathy
Published in Andrea Natale, Oussama M. Wazni, Kalyanam Shivkumar, Francis E. Marchlinski, Handbook of Cardiac Electrophysiology, 2020
Daniele Muser, Pasquale Santangeli
ARVC is a genetically determined cardiomyopathy with heterogeneous inheritance and clinical phenotype with variable penetrance and clinical severity of the disease among family trees. In up to 50% of the cases, a definite causal gene mutation cannot be found while desmosomal gene mutations are responsible for the disease in the 70% of cases with a positive genetic test.9 The first mutations causing the disease were found in 2000 in genes encoding for the desmosomal proteins plakoglobin and desmoplakin among patients with autosomal recessive Naxos and Carvajal cardiocutaneous syndromes, respectively.10–12 Both present woolly hair, keratoderma and arrhythmogenic cardiomyopathy with a higher incidence of LV involvement in the second one. Other desmosomal genes encoding for plakophilin, desmoglein, and desmocollin have also been discovered and have been associated to both autosomal recessive and dominant forms.13–15 In a lower proportion of cases, genes encoding for other non-desmosomal proteins like the ryanodine receptor and the transforming growth factor-β3 have been found.16,17 Mutations in the genes encoding for titin, lamin A/C and phospholamban have also been described and typically lead to arrhythmogenic syndromes characterized by a dilated cardiomyopathy phenotype overlapping with the classical ARVC phenotype.18–20
The Association of RGS2 and Slug in the Androgen-induced Acquisition of Mesenchymal Features of Breast MDA-MB-453 Cancer Cells
Published in Endocrine Research, 2022
Dana B. Alsafadi, Mohammad S. Abdullah, Randa Bawadi, Mamoun Ahram
It is interesting to note that inhibition of Slug expression does not reduce the DHT-induced migration of these cells. The separation of morphological-altering pathways from cell migration is not unprecedented and has previously been reported.41 This strongly suggests the involvement of divergent pathways once AR is activated. A potential pathway may proceed through Wnt/β-catenin/TCF4. The connection between AR signaling and the latter pathway is well established in prostate and breast cancers.42 In bladder cancer, activation of AR by DHT results in stimulation of the Wnt/β-catenin pathway marked by the nuclear translocation of β-catenin, which stimulates the expression of slug.27 However, the mesenchymal transformation of MDA-MB-453 cells is associated with the down-regulation of expression of β-catenin, N-cadherin, TCF4, and fibronectin and the lack of change in the expression of E-cadherin, vimentin, and ZEB1 and ZEB2 in DHT-treated MDA-MB-453 cells.12 Another possible mechanism is the suppression of the expression of desmocollin 2, which is essential for cell-cell adhesion and whose down-regulation induces MDA-MB-453 cells to assume a mesenchymal shape in association with a slight, but insignificant, increase in cell migration.43 The β-catenin pathway is still involved in regulating the function of desmocollin 2.
In-Silico Analysis of Differentially Expressed Genes and Their Regulating microRNA Involved in Lymph Node Metastasis in Invasive Breast Carcinoma
Published in Cancer Investigation, 2022
Anupama Modi, Purvi Purohit, Ashita Gadwal, Shweta Ukey, Dipayan Roy, Sujoy Fernandes, Mithu Banerjee
Desmocollin 3 (DSC3), a member of the cadherin superfamily of calcium-dependent cell adhesion molecules, is a desmosomal protein. DSC3 helps maintain tissue architecture; hence, their loss leads to a lack of adhesion and a gain of cellular mobility (29,30). DSC3 is a p53 responsive gene, and its expression is downregulated in BC cell lines and primary breast tumors, indicating that the loss of DSC3 expression is a common event in primary breast tumor specimens (29). In esophageal adenocarcinoma (EACs) tissue samples and human EAC cell lines, a significant downregulation (P < .001) of the DSC3 mRNA levels has been observed. Besides, the EAC cell lines and tumor samples had aberrant promoter hypermethylation as compared to normal esophageal samples (P < .001) (30). DSC3 has also been implicated in LNM and cellular proliferation in oral squamous cell carcinoma through the regulation of β-catenin (31). We have found DSC3 to be significantly downregulated in N1-N3 subgroups of LNM BC patients compared to normal breast tissue and the N0 subgroup (Supplementary Table S5).
Involvement of β-catenin in Androgen-induced Mesenchymal Transition of Breast MDA-MB-453 Cancer Cells
Published in Endocrine Research, 2021
Mamoun Ahram, Randa Bawadi, Mohammad S. Abdullah, Dana B. Alsafadi, Haneen Abaza, Sallam Abdallah, Ebtihal Mustafa
There is clearly a genomic effect associated with the DHT-induced mesenchymal transition of cells. Other than Slug, other effectors may be involved. For example, the possible contribution of the desmosomal protein, desmocollin 2, is intriguing as its reduction may destabilize cell–cell interaction and transform cell shape. Another means by which AR may induce the mesenchymal transition of cells is via microRNA molecules. We have reported earlier that, one, AR activation results in down-regulation of miR-125b in MDA-MB-453 cells, and, two, rescuing this microRNA negated the effect of DHT on cell morphology.33 Although changes in actin cytoskeleton were not noted following short-term treatment of cells with DHT, a noncanonical pathway(s) may still be important through AR activation of intracellular signaling molecules or via a membrane receptor. A study has shown that migration of MDA-MB-453 and MDA-MB-231 cells was stimulated by DHT in association with the formation of a complex between AR, Src, and phosphatidyl-3 kinase shortly after treatment with AR agonist.28 In the same study, it was suggested that this complex was likely responsible for increased migration, although no strong evidence was provided. A change in cell morphology into a mesenchymal form was also noted following treatment of MDA-MB-453 cells with membrane-impermeable testosterone indicating an action through a membrane receptor, although this requires further validation.70