The strong propensity of Cadherin‐23 for aggregation inhibits cell migration

Sannigrahi, Malay K.; Srinivas, C.; Deokate, Nilesh; Rakshit, Sabyasachi

doi:10.1002/1878-0261.12469

Cited by 25 publications

(36 citation statements)

References 41 publications

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“…A549 cells endogenously express Cdh23 (full‐length, variant‐1) . To check the functional significance of Cdh23 EC1‐2 concerning the full‐length construct, we measured the in vitro binding of A549 live cells on Cdh23 EC1‐2‐modified surfaces.…”

Section: Resultsmentioning

confidence: 99%

“…Cdh23 mediates stronger cell–cell adhesion via homophilic trans‐binding than classical E‐cadherin . The implication of such strong adhesion by Cdh23 in physiology is metastatic suppression . It, therefore, became imperative to decipher the structural basis of the strong adhesion.…”

Section: Discussionmentioning

confidence: 99%

“…While the physiological significance of nonclassical cadherin‐mediated cell–cell junction is well recognized, little is explored on their molecular structures. Cadherin‐23 (Cdh23) is one of the giant nonclassical cadherins that forms strong intercellular junctions in nearly 90% of healthy epithelial tissues including the brain, lymph node, kidney, gastrointestinal tract, testis, and skin (The Human Proteome Atlas) . The strong junction that is mediated by the homophilic trans‐interactions of Cdh23 serves as metastasis suppressor for solid cancers including sarcoma, adrenocortical carcinoma, and cervical cancer (The Cancer Genome Atlas, TCGA) .…”

Section: Introductionmentioning

confidence: 99%

“…Cadherin‐23 (Cdh23) is one of the giant nonclassical cadherins that forms strong intercellular junctions in nearly 90% of healthy epithelial tissues including the brain, lymph node, kidney, gastrointestinal tract, testis, and skin (The Human Proteome Atlas) . The strong junction that is mediated by the homophilic trans‐interactions of Cdh23 serves as metastasis suppressor for solid cancers including sarcoma, adrenocortical carcinoma, and cervical cancer (The Cancer Genome Atlas, TCGA) . Interestingly, Cdh23 is also known for its strong binding with protocadherin‐15 (Pcdh15) at the tips of stereocilia in neuroepithelial cells where the complex serves as gating spring under sound stimuli .…”

Section: Introductionmentioning

confidence: 99%

“…The strong junction that is mediated by the homophilic trans‐interactions of Cdh23 serves as metastasis suppressor for solid cancers including sarcoma, adrenocortical carcinoma, and cervical cancer (The Cancer Genome Atlas, TCGA) . Interestingly, Cdh23 is also known for its strong binding with protocadherin‐15 (Pcdh15) at the tips of stereocilia in neuroepithelial cells where the complex serves as gating spring under sound stimuli . While the structural detail of the heterophilic complex with Cdh23 is understood , the molecular details of the homophilic complex are not identified yet.…”

Section: Introductionmentioning

confidence: 99%

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Structural basis of the strong cell‐cell junction formed by cadherin‐23

et al. 2019

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Cadherin-23, a giant atypical cadherin, form homophilic interactions at the cell-cell junction of epithelial cells and heterophilic interactions with protocadherin-15 at the tip links of neuroepithelial cells. While the molecular structure of the heterodimer is solved, the homodimer structure is yet to be resolved. The homodimers play an essential role in cell-cell adhesion as the downregulation of cadherin-23 in cancers loosen the intercellular junction resulting in faster migration of cancer cells and a significant drop in patient survival. In vitro studies have measured a stronger aggregation propensity of cadherin-23 compared to typical E-cadherin. Here, we deciphered the unique trans-homodimer structure of cadherin-23 in solution and show that it consists of two electrostatic-based interfaces extended up to two terminal domains. The interface is robust, with a low off-rate of~8 9 10 À4 s À1 that supports its strong aggregation propensity. We identified a point mutation, E78K, that disrupts this binding. Interestingly, a mutation at the interface was reported in skin cancer. Overall, the structural basis of the strong cadherin-23 adhesion may have far-reaching applications in the fields of mechanobiology and cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Structural basis of the strong cell‐cell junction formed by cadherin‐23

et al. 2019

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Growing Human Dermal Fibroblasts as Spheroids Renders Them Susceptible for Early Expression of Pluripotency Genes

Raghunath²,

Lee

2019

Adv. Biosys.

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approaches have been adopted to coax cells in single cell suspension to aggregate and form spheroids, such as i) hanging drop culture, ii) growing cells on low-attachment culture surfaces, and iii) culturing cells in rotating bioreactors. The principle of these methods is to prevent cells from adhering to the cell culture vessel surface and instead encourage the cells to adhere to each other. This would then force the cells to form aggregates/spheroids, establish close cell-cell contacts and communication. Spheroid cultures are considered to be better suited for studying a wide range of cellular activities, such as tissue development and disease. [3] In the past decade, the use of spheroid culture to investigate cancer biology in vitro has increased significantly because it morphologically resembles a tumor. It has been reported that cancer cell spheroids mimic a more "realistic" cellular response to radioactive [4] and chemical [5] treatments than cancer cells maintained as 2-dimensional (2D) monolayer culture. Thus, cancer spheroids are emerging as a preferable model for identifying and translating new types of cancer therapies.Several studies have highlighted that the expression of numerous genes change when the same cell type is grown as spheroid instead of monolayer culture. These genes relate to cell differentiation and cell reprogramming, particularly key pluripotency genes Oct4, Sox2, and Nanog. This was observed in mouse embryonic stem cells, [6] human mesenchymal stem cells [7] (MSCs), human cancer cell lines, [8] and mouse fibroblasts. [9] Research has also revealed that spheroid cultures favors mesenchymal-to-epithelial transition (MET), maintenance and even induction of epithelial phenotypes in various cell types. [9][10][11] MET is an essential initiation step in stem cell reprogramming and thus dedifferentiation of mesenchymal lineage cell types. [12] Indeed, MSC spheroids have been reported to acquire enhanced multipotency so that the MSCs could differentiate into more diverse cell types. Cesarz and Tamama claimed that MSC cultured as spheroids were capable to differentiating into more lineages than otherwise possible when cultured as monolayer. [13] Together, these findings suggest the use spheroid cultures might induce spontaneous induction of dedifferentiation, and initial expression of pluripotency markers, and this might be useful at a later stage to increase reprogramming efficiency in the iPSC field.Suspension spheroid cultures of anchorage-dependent cell types have been widely used in cancer and stem cell research, as well as for producing organoids. It is believed that the 3-dimensional spheroid presents cells with a more physiological microenvironment to grow so that they behave more like cells in vivo, which is lacking in conventional 2-dimensional monolayer cultures. Recently, it has been reported that cancer cells grown as spheroids could express stem cell-associated genes. Hence, it is investigated whether normal mouse and human fibroblasts cultured as spheroids could also be induced...

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Multi-omics Analysis Classifies Colorectal Cancer into Distinct Methylated Immunogenic and Angiogenic Subtypes Based on Anatomical Laterality

Vatsyayan

Damodaran

et al. 2023

Indian J Surg Oncol

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The strong propensity of Cadherin‐23 for aggregation inhibits cell migration

Cited by 25 publications

References 41 publications

Structural basis of the strong cell‐cell junction formed by cadherin‐23

Structural basis of the strong cell‐cell junction formed by cadherin‐23

Growing Human Dermal Fibroblasts as Spheroids Renders Them Susceptible for Early Expression of Pluripotency Genes

Multi-omics Analysis Classifies Colorectal Cancer into Distinct Methylated Immunogenic and Angiogenic Subtypes Based on Anatomical Laterality

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