Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HDL and its major component, apolipoprotein A-I (apoA-I), play a central role in reverse cholesterol transport. We recently reported the involvement of a glycosylphosphatidylinositol anchor (GPI anchor) in the binding of HDL and apoA-I on human macrophages, and purified an 80 kDa HDL/apoA-I binding protein. In the present study, we characterized the GPI-anchored HDL/apoA-I binding protein from macrophages. The HDL/apoA-I binding protein was purified from macrophages and digested with endopeptidase, and the resultant fragments were sequenced. Cholesterol efflux, flow cytometry, immunoblotting, and immunohistochemical analyses were performed to characterize the HDL/apoA-I binding protein. Two parts of seven amino acid sequences completely matched those of moesin. Flow cytometry, immunoblotting, and immunohistochemistry using anti-moesin antibody showed that the HDL/apoA-I binding protein was N-glycosylated and expressed on the cell surface. It was termed moesin-like protein. Treatment of macrophages with anti-moesin antibody blocked the binding of HDL/apoA-I and suppressed cholesterol efflux. The moesin-like protein was exclusively expressed on macrophages and was upregulated by cholesterol loading and cell differentiation. Our results indicate that the moesin-like HDL/apoA-I binding protein is specifically expressed on the surface of human macrophages and promotes cholesterol efflux from macrophages.-Matsuyama, A, N. Sakai, H. Hiraoka, K-i. Hirano, and S. Yamashita. Cell surface-expressed moesin-like HDL/apoA-I binding protein promotes cholesterol efflux from human macrophages.
 ...
PMID:Cell surface-expressed moesin-like HDL/apoA-I binding protein promotes cholesterol efflux from human macrophages. 1625 20

A better molecular characterization of breast cell lines (BCL) may help discover new markers to apply to tumour samples. We performed gene and protein expression profiling of 31 BCL using whole-genome DNA microarrays and immunohistochemistry (IHC) on 'cell microarrays' (CMA), respectively. Global hierarchical clustering discriminated two groups of BCL: group I corresponded to luminal cell lines, group II to basal and mesenchymal cell lines. Correlations with centroids calculated from a published 'intrinsic 500-gene set' assigned 15 cell lines as luminal, eight as basal and four as mesenchymal. A set of 1.233 genes was differentially expressed between basal and luminal samples. Mesenchymal and basal subtypes were rather similar and discriminated by only 227 genes. The expression of 10 proteins (CAV1, CD44, EGFR, MET, ETS1, GATA3, luminal cytokeratin CK19, basal cytokeratin CK5/6, CD10, and ERM protein moesin) encoded by luminal vs basal discriminator genes confirmed the subtype classification and the validity of the identified markers. Our BCL basal/luminal signature correctly re-classified the published series of tumour samples that originally served to identify the molecular subtypes, suggesting that the identified markers should be useful for tumour classification and might represent promising targets for disease management.
 ...
PMID:Gene expression profiling of breast cell lines identifies potential new basal markers. 1628 5

CD44 is an important adhesion molecule that functions as the major hyaluronan receptor which mediates cell adhesion and migration in a variety of physiological and pathological processes. Although full activity of CD44 requires binding to ERM (ezrin/radixin/moesin) proteins, the CD44 cytoplasmic region, consisting of 72 amino acid residues, lacks the Motif-1 consensus sequence for ERM binding found in intercellular adhesion molecule (ICAM)-2 and other adhesion molecules of the immunoglobulin superfamily. Ultracentrifugation sedimentation studies and circular dichroism measurements revealed an extended monomeric form of the cytoplasmic peptide in solution. The crystal structure of the radixin FERM domain complexed with a CD44 cytoplasmic peptide reveals that the KKKLVIN sequence of the peptide forms a beta strand followed by a short loop structure that binds subdomain C of the FERM domain. Like Motif-1 binding, the CD44 beta strand binds the shallow groove between strand beta5C and helix alpha1C and augments the beta sheet beta5C-beta7C from subdomain C. Two hydrophobic CD44 residues, Leu and Ile, are docked into a hydrophobic pocket with the formation of hydrogen bonds between Asn of the CD44 short loop and loop beta4C-beta5C from subdomain C. This binding mode resembles that of NEP (neutral endopeptidase 24.11) rather than ICAM-2. Our results reveal a characteristic versatility of peptide recognition by the FERM domains from ERM proteins, suggest a possible mechanism by which the CD44 tail is released from the cytoskeleton for nuclear translocation by regulated intramembrane proteolysis, and provide a structural basis for Smad1 interactions with activated CD44 bound to ERM protein.
 ...
PMID:Structural basis for CD44 recognition by ERM proteins. 1875 40

Quantitative immunocytochemical assays of 1,200 breast carcinomas were assessed after construction of tissue microarrays. A total of 42 markers were evaluated for prognostic significance by univariate log rank test (mean follow-up, 79 months), using quantitative scoring by an image analysis device and specific software. Complete data were obtained for 924 patients, for whom 27 of the 42 markers proved to be significant prognostic indicators. Analysis of these 27 markers by logistic regression showed that 18 (cMet, CD44v6, FAK, moesin, caveolin, c-Kit, CK14, CD10, P21, P27, pMAPK, pSTAT3, STAT1, SHARP2, FYN, ER, PgR and c-erb B2), and 15 when ER, PgR and c-erb B2 were excluded, were 80.52% and 78.9% predictive of disease outcome, respectively. The immunocytochemical assays on 4 micron thick sections of fixed tissue are easy to handle in current practice and are cost-effective. Quantitative densitometric measurement of immunoprecipitates by computer-assisted devices from digitized microscopic images allows standardized high-throughput "in situ" molecular profiling within tumors. It is concluded that this 15 marker immunohistochemical signature is suitable for current practice, since performed on paraffin sections of fixed tumor samples, and can be used to select patients needing more aggressive therapy, since this signature is about 80% predictive of poor clinical outcome. Also, the markers included in the signature may be indicative of tumor responsiveness to current chemotherapy or suggest new targets for specific therapies.
 ...
PMID:A signature predictive of disease outcome in breast carcinomas, identified by quantitative immunocytochemical assays. 1914 69

We aimed in this study at identifying prognostic immunohistochemical molecular signatures indicative of disease outcome, also relevant for development of new specific therapies, in triple-negative (ER, PR, c-erbB2- negative) breast carcinoma subtypes. We evaluated 42 markers in tissue micro-arrays from a series of 924 breast carcinomas including 184 triple-negative tumors using standardized quantitative immunocytochemical assays and correlated the data with patients' outcome (mean follow-up of 79 months). When 27/42 markers including basal-like markers first found to be individually significant for prognosis in a univariate analysis (log-rank test) in 924 tumors, were secondly evaluated in the triple-negative tumor subtype (184/924), eleven including maspin, P21, P27, PTEN, caveolin, EGFR, FAK, P38, pMAPK, STAT1 and CD10 were 89.2% predictive of disease outcome in logistic regression. When markers reported in the literature as expressed in basal-like subtype were evaluated in the 924 series, only eight (EGFR, CK14, moesin, caveolin, cMet, ckit, CD44v6, C10) were prognosis predictive in univariate analysis (log-rank test) and in logistic regression were predictive of disease outcome in 66.3% independently of ER, PR and c-erbB2 expression and in 72% in triple-negative tumor subset. The results suggest that the category of 'triple-negative' breast carcinomas does not exactly overlap the basal-like subtype, and that immunoprofiling of triple-negative tumors (not similar to that of basal-like tumors) may be helpful to select patients for more aggressive treatment and provides a basis for development of tailored therapy.
 ...
PMID:Quantitative immunocytochemical profile to predict early outcome of disease in triple-negative breast carcinomas. 1928 55

Peptidases are emerging as promising drug targets in tumour suppression. Neprilysin, also known as neutral endopeptidase, is a cell surface peptidase that degrades various peptides such as angiotensin II, endothelin I, Substance P, etc., and reduces their local concentration. Neprilysin is expressed in various tissues such as kidney, prostate, lung, breast, brain, intestine, adrenal gland, etc. The tumour-suppressor mechanisms of neprilysin include its peptidase activity that degrades mitogenic growth factors such as fibroblast growth factor-2 and insulin-like growth factors, and the protein-protein interaction of neprilysin with phosphatase and tensin homolog, focal adhesion kinase, ezrin/radixin/moesin, and phosphoinositide 3-kinase. Studies have shown that the levels of neprilysin play an important role in malignancies. NEP is downregulated in prostate, renal, lung, breast, urothelial, cervical, hepatic cancers, etc. Histone deacetylation and hypermethylation of the neprilysin promoter region are the common mechanisms involved in the downregulation of neprilysin. Downregulation of the peptidase promotes angiogenesis, cell survival and cell migration. This review presents an overview of the role of neprilysin in malignancy, the tumour suppression mechanisms of neprilysin, the epigenetic mechanisms responsible for downregulation of neprilysin, and the potential pharmacological approaches to upregulate neprilysin levels and its activity.
 ...
PMID:Tumour suppression through modulation of neprilysin signaling: A comprehensive review. 3316 Sep 35