Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of the tight junction protein Junctional Adhesion Molecule-A (JAM-A) has been linked to aggressive disease in breast and other cancers, but JAM-targeting drugs remain elusive. Screening of a natural compound library identified the antibiotic Tetrocarcin-A as a novel downregulator of JAM-A and human epidermal growth factor receptor-2 (HER2) protein expression in breast cancer cells. Lysosomal inhibition partially rescued the downregulation of JAM-A and HER2 caused by Tetrocarcin-A, and attenuated its cytotoxic activity. Tetrocarcin-A treatment or JAM-A silencing reduced AKT and ERK phosphorylation, inhibited c-FOS phosphorylation at Threonine-232 (its transcriptional regulation site), inhibited nuclear localization of c-FOS, and downregulated expression of the inhibitor of apoptosis proteins (IAP). This was accompanied by Tetrocarcin-A-induced caspase-dependent apoptosis. To begin evaluating the potential clinical relevance of our findings, we extended our studies to other models. Encouragingly, Tetrocarcin-A downregulated JAM-A expression and caused cytotoxicity in primary breast cells and lung cancer stem cells, and inhibited the growth of xenografts in a semi-in vivo model involving invasion across the chicken egg chorioallantoic membrane. Taken together, our data suggest that Tetrocarcin-A warrants future evaluation as a novel cancer therapeutic by virtue of its ability to downregulate JAM-A expression, reduce tumorigenic signaling and induce apoptosis.
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PMID:Natural compound Tetrocarcin-A downregulates Junctional Adhesion Molecule-A in conjunction with HER2 and inhibitor of apoptosis proteins and inhibits tumor cell growth. 3031 28

Cell-cell adhesion plays a key role in the maintenance of the epithelial barrier and apicobasal cell polarity, which is crucial for homeostasis. Disruption of cell-cell adhesion is a hallmark of numerous pathological conditions, including invasive carcinomas. Adhesion between apposing cells is primarily regulated by three types of junctional structures: desmosomes, adherens junctions, and tight junctions. Cell junctional structures are highly regulated multiprotein complexes that also serve as signaling platforms to control epithelial cell function. The biogenesis, integrity, and stability of cell junctions is controlled by complex regulatory interactions with cytoskeletal and polarity proteins, as well as modulation of key component proteins by phosphorylation/dephosphorylation processes. Not surprisingly, many essential signaling molecules, including protein Ser/Thr phosphatase 2A (PP2A) are associated with intercellular junctions. Here, we examine how major PP2A enzymes regulate epithelial cell-cell junctions, either directly by associating with and dephosphorylating component proteins, or indirectly by affecting signaling pathways that control junctional integrity and cytoskeletal dynamics. PP2A deregulation has severe consequences on the stability and functionality of these structures, and disruption of cell-cell adhesion and cell polarity likely contribute to the link between PP2A dysfunction and human carcinomas.
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PMID:Protein Phosphatase 2A: More Than a Passenger in the Regulation of Epithelial Cell-Cell Junctions. 3089 76

Adhesion is the foremost step in pathogenesis and biofilm formation and is facilitated by a special class of cell wall proteins known as adhesins. Formation of biofilms in catheters and other medical devices subsequently leads to infections. As compared to bacterial adhesins, there is relatively less work for the characterization and identification of fungal adhesins. Understanding the sequence characterization of fungal adhesins may facilitate a better understanding of its role in pathogenesis. Experimental methods for investigation and characterization of fungal adhesins are labor intensive and expensive. Therefore, there is a need for fast and efficient computational methods for the identification and characterization of fungal adhesins. The aim of the current study is twofold: (i) to develop an accurate predictor for fungal adhesins, (ii) to sieve out the prominent molecular signatures present in fungal adhesins. Of the many supervised learning algorithms implemented in the current study, voting ensembles resulted in enhanced prediction accuracy. The best voting-ensemble consisting of three support vector machines with three different kernels (PolyK, RBF, PuK) achieved an accuracy of 94.9% on leave one out cross validation and 98.0% accuracy on blind testing set. A preference/avoidance list of molecular features as well as human interpretable rules are also extracted giving insights into the general sequence features of fungal adhesins. Fungal adhesins are characterized by high Threonine and Cysteine and avoidance for Phenylalanine and Methionine. They also have avoidance for average hydrophilicity. The current analysis possibly will facilitate the understanding of the mechanism of fungal adhesin function which may further help in designing methods for restricting adhesin mediated pathogenesis.
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PMID:Prediction and molecular insights into fungal adhesins and adhesin like proteins. 3107 12


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