Cadherin

Summary

Cadherins (named for "calcium-dependent adhesion") are cell adhesion molecules important in forming adherens junctions that let cells adhere to each other. Cadherins are a class of type-1 transmembrane proteins, and they depend on calcium (Ca2+) ions to function, hence their name. Cell-cell adhesion is mediated by extracellular cadherin domains, whereas the intracellular cytoplasmic tail associates with numerous adaptors and signaling proteins, collectively referred to as the cadherin adhesome. Background The cadherin family is essential in maintaining cell-cell contact and regulating cytoskeletal complexes. The cadherin superfamily includes cadherins, protocadherins, desmogleins, desmocollins, and more. In structure, they share cadherin repeats, which are the extracellular Ca2+-binding domains. There are multiple classes of cadherin molecules, each designated with a prefix for tissues with which it associates. Classical cadherins maintain the tone of tissues by forming a h

Official source

https://en.wikipedia.org/wiki/Cadherin

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Self-organization is a dynamic and lineage-intrinsic property of mammary epithelial cells

Léa Chanson

Loss of organization is a principle feature of cancers; therefore it is important to understand how normal adult multilineage tissues, such as bilayered secretory epithelia, establish and maintain their architectures. The self-organization process that drives heterogeneous mixtures of cells to form organized tissues is well studied in embryology and with mammalian cell lines that were abnormal or engineered. Here we used a micropatterning approach that confined cells to a cylindrical geometry combined with an algorithm to quantify changes of cellular distribution over time to measure the ability of different cell types to self-organize relative to each other. Using normal human mammary epithelial cells enriched into pools of the two principal lineages, luminal and myoepithelial cells, we demonstrated that bilayered organization in mammary epithelium was driven mainly by lineage-specific differential E-cadherin expression, but that P-cadherin contributed specifically to organization of the myoepithelial layer. Disruption of the actomyosin network or of adherens junction proteins resulted in either prevention of bilayer formation or loss of preformed bilayers, consistent with continual sampling of the local microenvironment by cadherins. Together these data show that self-organization is an innate and reversible property of communities of normal adult human mammary epithelial cells.

2011

Collective cell migration of epithelial tumor cells is one of the important factors for elucidating cancer metastasis and developing novel drugs for cancer treatment. Especially, new roles of E-cadherin in cancer migration and metastasis, beyond the epithelial-mesenchymal transition, have recently been unveiled. Here, we quantitatively examined cell motility using micropatterned free edge migration model with E-cadherin re-expressing EC96 cells derived from adenocarcinoma gastric (AGS) cell line. EC96 cells showed increased migration features such as the expansion of cell islands and straightforward movement compared to AGS cells. The function of tight junction proteins known to E-cadherin expression were evaluated for cell migration by knockdown using sh-RNA. Cell migration and straight movement of EC96 cells were reduced by knockdown of ZO-1 and claudin-7, to a lesser degree. Analysis of the migratory activity of boundary cells and inner cells shows that EC96 cell migration was primarily conducted by boundary cells, similar to leader cells in collective migration. Immunofluorescence analysis showed that tight junctions (TJs) of EC96 cells might play important roles in intracellular communication among boundary cells. ZO-1 is localized to the base of protruding lamellipodia and cell contact sites at the rear of cells, indicating that ZO-1 might be important for the interaction between traction and tensile forces. Overall, dynamic regulation of E-cadherin expression and localization by interaction with ZO-1 protein is one of the targets for elucidating the mechanism of collective migration of cancer metastasis.

MDPI2021

Probing the differential adhesion hypothesis in the mammary gland using different bioengineered cell culture substrata

Léa Chanson

During tissue development, cells are able to form different layers and to self organize. At the moment, there are two principal hypotheses that try to explain cell sorting. The so called differential adhesion hypothesis (DAH) posits that cells organize according to the level of expression of cell-cell adhesion proteins so as to reduce free-energy in the system. The second hypothesis explains the formation of different germ layers according to cortical tension among cells of distinct phenotypes. For this work, we wanted to study cell sorting in the mammary glands, which are bilayered branching structures composed of outer myoepithelial (MEP) and inner luminal epithelial cells (LEP). Both sorting hypotheses were tested using bioengineered cell culture substrata. Using arrays of micro-wells that were cast in polydimethylsiloxane (PDMS) coupled with quantitative image analysis, we observed that cell sorting occurred over time between LEP and MEP that were isolated by fluorescence-activated cell sorting from primary human mammary epithelial cells. Inhibitors of specific cadherins were able to prevent cell sorting in accordance with the DAH. However, chemical inhibitors of cytoskeletal proteins, which effectively prevented the cells from modulating their innate elasticity, also prevented cell sorting suggesting cortical tension also plays an important role. Thus, our data suggests a third hypothesis, which is essentially a unification of the original two, such that differences in cortical tension are essentially lineage-specific and are governed wholly or in-part by cell-cell adhesion molecules. Experimental resolution of this hypothesis is being actively pursued

2009