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Accumulation of abnormal chondroitin sulfate (CS) chains in breast cancer tissue is correlated with poor prognosis. However, the biological functions of these CS chains in cancer progression remain largely unknown, impeding the development of targeted treatment focused on CS. Previous studies identified chondroitin polymerizing factor (CHPF; also known as chondroitin sulfate synthase 2) is the critical enzyme regulating CS accumulation in breast cancer tissue. We then assessed the association between CHPF‐associated proteoglycans (PGs) and signaling pathways in breast cancer datasets. The regulation between CHPF and syndecan 1 (SDC1) was examined at both the protein and RNA levels. Confocal microscopy and image flow cytometry were employed to quantify macropinocytosis. The effects of the 6‐O‐sulfated CS‐binding peptide (C6S‐p) on blocking CS functions were tested in vitro and in vivo. Results indicated that the expression of CHPF and SDC1 was tightly associated within primary breast cancer tissue, and high expression of both genes exacerbated patient prognosis. Transforming growth factor beta (TGF‐β) signaling was implicated in the regulation of CHPF and SDC1 in breast cancer cells. CHPF supported CS–SDC1 stabilization on the cell surface, modulating macropinocytotic activity in breast cancer cells under nutrient‐deprived conditions. Furthermore, C6S‐p demonstrated the ability to bind CS‐SDC1, increase SDC1 degradation, suppress macropinocytosis of breast cancer cells, and inhibit tumor growth in vivo. Although other PGs may also be involved in CHPF‐regulated breast cancer malignancy, this study provides the first evidence that a CS synthase participates in the regulation of macropinocytosis in cancer cells by supporting SDC1 expression on cancer cells. [ABSTRACT FROM AUTHOR]

B4GALT3 epxression is negatively correlated with advanced stages and tumor metastasis in CRC patients. B4GALT3 regulates cell invsiveness through altering β1 integrin activation and glycan structures.Metastasis often occurs in colorectal cancer (CRC) patients and is the main difficulty in cancer treatment. The upregulation of poly-N-acetyllactosamine-related glycosylation is found in CRC patients and is associated with progression and metastasis in cancer. β-1,4-Galactosyltransferase III (B4GALT3) is an enzyme responsible for poly-N-acetyllactosamine synthesis, and therefore, we investigated its expression in CRC patients. We found that B4GALT3 negatively correlated with poorly differentiated histology (P < 0.001), advanced stages (P = 0.0052), regional lymph node metastasis (P = 0.0018) and distant metastasis (P = 0.0463) in CRC patients. B4GALT3 overexpression in CRC cells suppressed cell migration, invasion and adhesion, whereas B4GALT3 knockdown enhanced malignant cell phenotypes. The β1 integrin-blocking antibody reversed the B4GALT3-mediated increase in cell invasion. B4GALT3 expression altered glycosylation on the N-glycan of β1 integrin probably through changes in poly-N-acetyllactosamine expression. Furthermore, more activated β1 integrin along with the activation of its downstream signaling transduction were found in B4GALT3 knockdown cells, whereas overexpression of B4GALT3 suppressed the expression of active β1 integrin and inhibited its downstream signaling. Our results suggest that B4GALT3 is negatively associated with CRC metastasis and suppresses cell invasiveness through inhibiting activation of β1 integrin. [ABSTRACT FROM AUTHOR]

Infantile hemangiomas are localized lesions comprised primarily of aberrant endothelial cells. COSMC plays a crucial role in blood vessel formation and is characterized as a molecular chaperone of T-synthase which catalyzes the synthesis of T antigen (Galβ1,3GalNAc). T antigen expression is associated with tumor malignancy in many cancers. However, roles of COSMC in infantile hemangioma are still unclear. In this study, immunohistochemistry showed that COSMC was upregulated in proliferating hemangiomas compared with involuted hemangiomas. Higher levels of T antigen expression were also observed in the proliferating hemangioma. Overexpression of COSMC significantly enhanced cell growth and phosphorylation of AKT and ERK in human umbilical vein endothelial cells (HUVECs). Conversely, knockdown of COSMC with siRNA inhibited endothelial cell growth. Mechanistic investigation showed that O-glycans were present on VEGFR2 and these structures were modulated by COSMC. Furthermore, VEGFR2 degradation was delayed by COSMC overexpression and facilitated by COSMC knockdown. We also showed that COSMC was able to regulate VEGF-triggered phosphorylation of VEGFR2. Our results suggest that COSMC is a novel regulator for VEGFR2 signaling in endothelial cells and dysregulation of COSMC expression may contribute to the pathogenesis of hemangioma. [ABSTRACT FROM AUTHOR]

The densification, crystallization, and dielectric/ferroelectric properties of a SrO–BaO–Nb2O5–SiO2 glass-ceramic were investigated. Glass-ceramics containing (Sr, Ba)Nb2O6 tungsten bronze as the major crystalline phase can be sintered below 1000 °C. The good sinterability is attributed to that the major crystallization process occurred after the sintering of the glass powder compact. The variations of dielectric properties with sintering temperature and test frequency can be explained qualitatively by the amount of SBN phase formed. The maximum dielectric constant at 1 kHz is about 351 for the glass-ceramic sintered at 1000 °C. The existence of ferroelectricity is verified for the present glass-ceramic. The values of the remanent polarization and the coercive field are about 0.15 μC/cm2 and 4.5 kV/cm, respectively, for the glass-ceramic sintered at 1000 °C. [Copyright &y& Elsevier]

The study presents micro- and nano-structures forming a flexible gas sensor based on combinative coating and ultrashort-pulse laser techniques in graphene/silver nanoparticles (G-Ag) thin film electrodes on polyimide (PI) substrate. The prepared silver nanoparticles (AgNPs) revealed the nano-microstructures retain the characteristics of graphene (G). The irregularly distributed AgNPs were deposited on the surface of G sheets, promoting the formation of stacked porous structures with high specific surface area between the AgNPs and G sheets. Under temperature-assisted control, G-Ag composite structures with high sensitivity (response) and selectivity increase gas detection of nitric oxide (NO). This is due to the high adsorption capacity and stability of AgNPs for NO gas molecules, and therefore G-Ag thin film on flexible substrate is a potential sensor for gas detection. [ABSTRACT FROM AUTHOR]

Carboxyl‐terminus of Hsc70 interacting protein (CHIP) is a chaperone‐dependent E3‐ubiquitin ligase with important function in protein quality control system. In the current research endeavor, we have investigated the putative role of CHIP in lipopolysaccharides (LPS)‐induced cardiomyopathies. Basically, H9c2 cardiomyoblasts were transfected with CHIP for 24 hr, and thereafter, treated with LPS for 12 hr. Concomitantly, western blot analysis, actin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and coimmunoprecipitation studies were performed to investigate the underlying intricacies. Interestingly, western blot analysis revealed that the expression of hypertrophy and apoptosis‐related proteins were considerably reduced following overexpression of CHIP. Moreover, Actin staining and TUNEL assay further ascertained the attenuation of cardiac hypertrophy and apoptosis following overexpression of CHIP respectively. These aspects instigate the role of CHIP in attenuation of LPS‐induced cardiomyopathies. Additionally and importantly, co‐immunoprecipitation and western blot studies revealed that CHIP plausibly promotes degradation of nuclear factor of activated T cells 3 (NFATc3) through ubiquitin‐proteasomal pathway. Taken together, our study reveals that CHIP attenuates LPS‐induced cardiac hypertrophy and apoptosis perhaps by promoting NFATc3 proteasomal degradation. [ABSTRACT FROM AUTHOR]

The methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) is associated with the prognosis in gliomas and in other cancers. Recent studies showed that rs16906252, an SNP in the MGMT promoter, is associated with promoter methylation and is a predictor of the overall survival time (OST) and the response to temozolomide (TMZ) treatment. However, these findings haven’t been systematically investigated in the Han-Chinese population. We analyzed the relevance between rs16906252 polymorphisms, the MGMT methylation status, and the OST in 72 Han-Chinese gliomas patients. The MGMT promoter methylation was measured by bisulfite conversion followed by pyro-sequencing, while rs16906252 was measured by restriction endonuclease digestion. Contrary to the previous findings, we found no association between rs16906252 genotypes and promoter methylation on MGMT. The lower-grade glioma (LGGs) patients carrying the C allele with rs16906252 showed a surprisingly better OST (P = 0.04). Furthermore, the LGG patients carrying hypo-methylated MGMT promoter and rs16906252 T allele showed significantly poorer prognosis. The prognostic benefit of MGMT promoter methylation and genotypes on gliomas patients is marginal. A new molecular stratified patient grouping of LGGs is potentially associated with poorer OST. Active MGMT might have a protective role in LGG tumors, enabling evolution to severe malignancy. [ABSTRACT FROM AUTHOR]

Cancer cell invasion and metastasis are the primary causes of treatment failure and death in hepatocellular carcinoma (HCC). We previously reported that core 1 β1,3-galactosyltransferase (C1GALT1) is frequently overexpressed in HCC tumors and its expression is associated with advanced tumor stage, metastasis, and poor survival. However, the underlying mechanisms of C1GALT1 in HCC malignancy remain unclear. In this study, we found that overexpression of C1GALT1 enhanced HCC cell adhesion to extracellular matrix (ECM) proteins, migration, and invasion, whereas RNAi-mediated knockdown of C1GALT1 suppressed these phenotypes. The promoting effect of C1GALT1 on the metastasis of HCC cells was demonstrated in a mouse xenograft model. Mechanistic investigations showed that the C1GALT1-enhanced phenotypic changes in HCC cells were significantly suppressed by anti-integrin β1 blocking antibody. Moreover, C1GALT1 was able to modify O-glycans on integrin β1 and regulate integrin β1 activity as well as its downstream signaling. These results suggest that C1GALT1 could enhance HCC invasiveness through integrin β1 and provide novel insights into the roles of O-glycosylation in HCC metastasis. [ABSTRACT FROM AUTHOR]