Cell Adhesion Molecules in Plasticity and Metastasis.
Ontology highlight
ABSTRACT:
SUBMITTER: Smart JA
PROVIDER: S-EPMC7785660 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:miR-19b is a key molecule for cancer development, however its crucial roles in breast cancer metastasis are rarely studied right now. In this study, using several bioinformatics databases to predict the downstream targets for miR-19b, we verified that a novel target gene, myosin regulatory light chain interacting protein (MYLIP), could be directly down-regulated by miR-19b through its 3'-UTR region. MYLIP belongs to the cytoskeletal protein clusters and is involved in the regulation of cell movement and migration. We further explored that miR-19b was highly expressed and negatively correlated with MYLIP expression in breast cancer patient samples from the TCGA database. And the over-expression of miR-19b or inhibition of MYLIP facilitated the migration and metastasis of breast cancer cells, through conducting the wound healing assay and transwell invasion assay. Additionally, miR-19b could obviously promote breast tumor growth in mouse models and affect the expressions of cell adhesion molecules (including E-Cadherin, ICAM-1 and Integrin ?1) by down-regulating E-Cadherin expression and up-regulating ICAM-1 and Integrin ?1 expressions in vitro and in vivo. Meanwhile, miR-19b effectively activated the Integrin ? downstream signaling pathways (such as the Ras-MAPK pathway and the PI3K-AKT pathway) and elevated the expression levels of essential genes in these two pathways. Taken together, these findings comprehensively illustrate the regulatory mechanisms ofmiR-19b in breast cancer metastasis, and provide us new insights for exploring MYLIP and its related cell adhesion molecules as promising therapeutic targets to interfere breast cancer development.
| S-EPMC5610006 | biostudies-literature
Project description:BackgroundCellular adhesion molecules (CAMs), which are normally associated with leukocyte trafficking, have also been shown to play an essential role in tumor metastasis to non-CNS sites. However, the role played by CAMs in brain metastasis is largely unexplored. It is known that leukocyte recruitment to the brain is very atypical and that mechanisms of disease in peripheral tissues cannot be extrapolated to the brain. Here, we have established the spatiotemporal expression of 12 key CAMs in the initial phases of tumor seeding in 2 different models of brain metastasis.MethodsBALB/c or SCID mice were injected intracardially (10(5) cells/100 ?L phosphate-buffered saline with either 4T1-GFP or MDA231BR-GFP cells, respectively (n = 4-6/group), and expression of the CAMs was determined by immunohistochemistry and immunofluorescence colocalisation.ResultsEndothelial expression of E-selectin, VCAM-1, ALCAM, ICAM-1, VLA-4, and ?4 integrin was markedly increased early in tumor seeding. At the same time, the natural ligands to these adhesion molecules were highly expressed on the metastatic tumor cells both in vitro and in vivo. Two of these ligands showed particularly high tumor cell expression (ALCAM and VLA-4), and consequently their functional role in tumor seeding was determined. Antibody neutralization of either ALCAM or VLA-4 significantly reduced tumor seeding within the brain (>60% decrease in tumor number/mm(2) brain; P < .05-0.01).ConclusionsThese findings suggest that ALCAM/ALCAM and VLA-4/VCAM-1 interactions play an important functional role in the early stages of metastasis seeding in the brain. Moreover, this work identifies a specific subset of ligand-receptor interactions that may yield new therapeutic and diagnostic targets for brain metastasis.
| S-EPMC3956349 | biostudies-literature
Project description:Cell adhesion molecules (CAMs) of the cadherin, integrin, immunoglobulin, and selectin protein families are indispensable for the formation and maintenance of multicellular tissues, especially epithelia. In the epidermis, they are involved in cell-cell contacts and in cellular interactions with the extracellular matrix (ECM), thereby contributing to the structural integrity and barrier formation of the skin. Bulk and single cell RNA sequencing data show that >170 CAMs are expressed in the healthy human skin, with high expression levels in melanocytes, keratinocytes, endothelial, and smooth muscle cells. Alterations in expression levels of CAMs are involved in melanoma propagation, interaction with the microenvironment, and metastasis. Recent mechanistic analyses together with protein and gene expression data provide a better picture of the role of CAMs in the context of skin physiology and melanoma. Here, we review progress in the field and discuss molecular mechanisms in light of gene expression profiles, including recent single cell RNA expression information. We highlight key adhesion molecules in melanoma, which can guide the identification of pathways and strategies for novel anti-melanoma therapies.
| S-EPMC8391223 | biostudies-literature
Project description:BackgroundMyofasciitis is a heterogeneous group of diseases pathologically characterized by inflammatory cell infiltration into the fascia. Endothelial activation plays a critical role in the pathogenesis of the inflammatory response. However, the expression of cellular adhesion molecules (CAMs) in myofasciitis has not been investigated.MethodsData on clinical features, thigh magnetic resonance imaging, and muscle pathology were collected from five patients with myofasciitis. Immunohistochemical (IHC) staining and Western blot (WB) of the muscle biopsies from patients and healthy controls were performed.ResultsIncreased levels of serum pro-inflammatory cytokines, including IL-6, TNF-α, and IL-2R, were detected in four patients. IHC staining and WB indicated significantly increased expression of cell adhesion molecules in blood vessels or inflammatory cells within the perimysium in muscle and fascia tissues of patients with myofasciitis compared to controls.ConclusionThe up-regulation of CAMs in myofasciitis indicates endothelial activation, which may be potential therapy targets for the treatment of myofasciitis.
| S-EPMC10203699 | biostudies-literature
Project description:Cell adhesion molecules are ubiquitous in multicellular organisms, specifying precise cell-cell interactions in processes as diverse as tissue development, immune cell trafficking and the wiring of the nervous system1-4. Here we show that a wide array of synthetic cell adhesion molecules can be generated by combining orthogonal extracellular interactions with intracellular domains from native adhesion molecules, such as cadherins and integrins. The resulting molecules yield customized cell-cell interactions with adhesion properties that are similar to native interactions. The identity of the intracellular domain of the synthetic cell adhesion molecules specifies interface morphology and mechanics, whereas diverse homotypic or heterotypic extracellular interaction domains independently specify the connectivity between cells. This toolkit of orthogonal adhesion molecules enables the rationally programmed assembly of multicellular architectures, as well as systematic remodelling of native tissues. The modularity of synthetic cell adhesion molecules provides fundamental insights into how distinct classes of cell-cell interfaces may have evolved. Overall, these tools offer powerful abilities for cell and tissue engineering and for systematically studying multicellular organization.
| S-EPMC9892004 | biostudies-literature
Project description:Thus far, understanding how the confined cellular environment affects the lifetime of bonds, as well as the extraction of complexation rates, has been a major challenge in studies of cell adhesion. Based on a theoretical description of the growth curves of adhesion domains, we present a new (to our knowledge) method to measure the association rate k(on) of ligand-receptor pairs incorporated into lipid membranes. As a proof of principle, we apply this method to several systems. We find that the k(on) for the interaction of biotin with neutravidin is larger than that for integrin binding to RGD or sialyl Lewis(x) to E-selectin. Furthermore, we find k(on) to be enhanced by membrane fluctuations that increase the probability for encounters between the binders. The opposite effect on k(on) could be attributed to the presence of repulsive polymers that mimic the glycocalyx, which points to two potential mechanisms for controlling the speed of protein complexation during the cell recognition process.
| S-EPMC4255260 | biostudies-literature
Project description:To identify cell adhesion molecules (CAMs) targeting bacterial membrane proteins within a synthetic bacteria-displayed nanobody library, we present a comprehensive whole-cell screening platform. This involves targeted amplicon sequencing to discover nanobodies targeting the natural adhesin, TraN. Furthermore, we employ deep mutational engineering to enhance the binding affinity of these nanobodies toward TraN.
2023-12-18 | GSE249103 | GEO
Project description:The occurrence of highly conserved amyloid-forming sequences in Candida albicans Als proteins (H. N. Otoo et al., Eukaryot. Cell 7:776-782, 2008) led us to search for similar sequences in other adhesins from C. albicans and Saccharomyces cerevisiae. The beta-aggregation predictor TANGO found highly beta-aggregation-prone sequences in almost all yeast adhesins. These sequences had an unusual amino acid composition: 77% of their residues were beta-branched aliphatic amino acids Ile, Thr, and Val, which is more than 4-fold greater than their prevalence in the S. cerevisiae proteome. High beta-aggregation potential peptides from S. cerevisiae Flo1p and C. albicans Eap1p rapidly formed insoluble amyloids, as determined by Congo red absorbance, thioflavin T fluorescence, and fiber morphology. As examples of the amyloid-forming ability of the native proteins, soluble glycosylphosphatidylinositol (GPI)-less fragments of C. albicans Als5p and S. cerevisiae Muc1p also formed amyloids within a few days under native conditions at nM concentrations. There was also evidence of amyloid formation in vivo: the surfaces of cells expressing wall-bound Als1p, Als5p, Muc1p, or Flo1p were birefringent and bound the fluorescent amyloid-reporting dye thioflavin T. Both of these properties increased upon aggregation of the cells. In addition, amyloid binding dyes strongly inhibited aggregation and flocculation. The results imply that amyloid formation is an intrinsic property of yeast cell adhesion proteins from many gene families and that amyloid formation is an important component of cellular aggregation mediated by these proteins.
| S-EPMC2837979 | biostudies-literature
Project description:Homophilic interaction of the L1 family of cell adhesion molecules plays a pivotal role in regulating neurite outgrowth and neural cell networking in vivo. Functional defects in L1 family members are associated with neurological disorders such as X-linked mental retardation, multiple sclerosis, low-IQ syndrome, developmental delay, and schizophrenia. Various human tumors with poor prognosis also implicate the role of L1, a representative member of the L1 family of cell adhesion molecules, and ectopic expression of L1 in fibroblastic cells induces metastasis-associated gene expression. Previous studies on L1 homologs indicated that four N-terminal immunoglobulin-like domains form a horseshoe-like structure that mediates homophilic interactions. Various models including the zipper, domain-swap, and symmetry-related models are proposed to be involved in structural mechanism of homophilic interaction of the L1 family members. Recently, cryo-electron tomography of L1 and crystal structure studies of neurofascin, an L1 family protein, have been performed. This review focuses on recent discoveries of different models and describes the possible structural mechanisms of homophilic interactions of L1 family members. Understanding structural mechanisms of homophilic interactions in various cell adhesion proteins should aid the development of therapeutic strategies for L1 family cell adhesion molecule-associated diseases.
| S-EPMC3406286 | biostudies-literature
Project description:There has been extensive research on structure and function of fungal cell adhesion molecules, but the most of the work has been about adhesins in Candida albicans and Saccharomyces cerevisiae. These yeasts are members of a single ascomycete order, and adhesion molecules from the six other fungal phyla are only sparsely described in the literature. In these other phyla, most of the research is at the cellular level, rather than at the molecular level, so there has been little characterization of the adhesion molecules themselves. A catalog of known adhesins shows some common features: high Ser/Thr content, tandem repeats, N- and O-glycosylations, GPI anchors, dibasic sequence motifs, and potential amyloid-forming sequences. However, none of these features is universal. Known ligands include proteins and glycans on homologous cells and host cells. Existing and novel tools can exploit the availability of genome sequences to identify and characterize new fungal adhesins. These include bioinformatics tools and well-established yeast surface display models, which could be coupled with an adhesion substrate array. Thus, new knowledge could be exploited to answer key questions in fungal ecology, animal and plant pathogenesis, and roles of biofilms in infection and biomass turnover.
| S-EPMC6023273 | biostudies-literature