Shifted Golgi targeting of glycosyltransferases and α-mannosidase IA from giantin to GM130-GRASP65 results in formation of high mannose N -glycans in aggressive prostate cancer cells

Bhat, Ganapati; Hothpet, Vishwanath Reddy; Lin, Ming‐Fong; Cheng, Pi-Wan

doi:10.1016/j.bbagen.2017.08.006

Cited by 19 publications

(17 citation statements)

References 39 publications

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“…In our study, high-mannose (M9) and core-fucosylated (FA2G2S1) plasma glycan species were significantly decreased in the PTSD group, compared to the low-stress healthy control, and this result corresponds to lower glycan species found in inflammation [34]. As alternations of high-mannose glycans have been associated with occurrence and progression of different types of cancers [38][39][40], neuropsychiatric disorders [41], inflammation [34] and brain aging [42], whereas PTSD is associated with inflammation [17] and cardiometabolic disorders [4,5], the lower FA2G2S1 glycan result suggests that veterans with PTSD should be closely monitored for these disorders.…”

Section: N-glycans In Plasmasupporting

confidence: 47%

N-glycomic Profile in Combat Related Post-Traumatic Stress Disorder

et al. 2019

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Post-traumatic stress disorder (PTSD) develops in a portion of individuals exposed to extreme trauma. Glycosylation is a post-translational modification that affects protein functions and is altered in various pathophysiological states and aging. There are still no validated biomarkers of PTSD. The aim of this study was to evaluate the N-glycomic profile in 543 male Caucasian individuals (299 veterans with PTSD and 244 control subjects). The study included discovery (N = 233) and replication (N = 310) cohort. Hydrophilic interaction HPLC and ultra-performance liquid chromatography were used to separate and detect 39 plasma and 24 IgG N-glycan species, respectively. All results were corrected for the effects of age and multiple testing. Significant results included only significantly altered N-glycans in cases/controls in both cohorts, in the same direction. Results showed that six plasma N-glycans (four increased and two decreased) were altered in PTSD vs. controls in both cohorts, but IgG N-glycans were similar between groups. The severity of PTSD was not associated with different plasma N-glycans. This is the first study detecting alterations in plasma N-glycans in PTSD. These N-glycans are also associated with other neuropsychiatric disorders and inflammation, suggesting possible shared glycosylation mechanisms.

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Section: N-glycans In Plasmasupporting

confidence: 47%

N-glycomic Profile in Combat Related Post-Traumatic Stress Disorder

et al. 2019

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“…The glycosyltransferases family proteins have been reported to be fundamentally involved in regulating several basic biologic processes, such as cell development, cell migration and invasion and carcinogenesis [ 21 , 30 – 32 ]. For example, anomalous glycosylation is a hallmark of several cancers, including ovarian cancer, that promote tumor progression and metastasis [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of glycosyltransferase 8 domain containing 2 confers ovarian cancer to CDDP resistance by activating FGFR/PI3K signalling axis

et al. 2021

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It has been reported that chemotherapy resistance mainly contributed to treatment failure and poor survival in patients with ovarian cancer. Therefore, clarifying the molecular mechanism and identifying effective strategies to overcome drug resistance may play an important clinical impact on this malignant tumor. In our study, we found that the expression of Glycosyltransferase 8 domain containing 2 (GLT8D2) was significantly upregulated in ovarian cancer samples with CDDP (Cis-dichlorodiammine-platinum) resistance. Biological experiment demonstrate that GLT8D2 overexpression confers CDDP resistance on ovarian cancer cells; however, inhibition of GLT8D2 sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. By using affinity purification/mass spectrometry (IP/MS) and reciprocal co-immunoprecipitation (co-IP) analyses, we found that GLT8D2 interacts with fibroblast growth factor receptor 1(FGFR1) in ovarian cancer cells. Furthermore, overexpression of GLT8D2 activated FGFR/PI3K signaling axis and upregulated the phosphorylation levels of FRS2a and AKT (AKT serine/threonine kinase). Importantly, pharmacological inhibition of FGFR and PI3K (phosphatidylinositol 3-kinase) signaling pathway significantly counteracted GLT8D2-induced chemoresistance and enhanced platinum’s therapeutic efficacy in ovarian cancer. Therefore, our findings suggest that GLT8D2 is a potential therapeutic target for the treatment of ovarian cancer; targeting GLT8D2/FGFR/PI3K/AKT signaling axis may represent a promising strategy to enhance platinum response in patients with chemoresistant ovarian cancer.

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“…GOLGB1 knockdown decreases protein concentration and induces mislocalization of many glycosyltransferases, such as B4GALT1, MGAT1, and ST6GAL1, 109 and shifts N-glycans toward a high-mannose type in cancer cell lines. 110 The O-glycosylation appears to be disturbed as well given that TMF1 maintains Golgi localization of GalNAc-T2 93 and knockdown of ZFPL1 decreases O-linked N-acetylglucosamine. 166 In this context, a carbohydrate analysis of mAb is necessary to confirm a disturbed glycosylation in detriment to O-glycan and complex N-glycan patterns in the higher producer cells.…”

Section: Discussionmentioning

confidence: 99%

Compartmentalized Proteomic Profiling Outlines the Crucial Role of the Classical Secretory Pathway during Recombinant Protein Production in Chinese Hamster Ovary Cells

et al. 2021

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Different cellular processes that contribute to protein production in Chinese hamster ovary (CHO) cells have been previously investigated by proteomics. However, although the classical secretory pathway (CSP) has been well documented as a bottleneck during recombinant protein (RP) production, it has not been well represented in previous proteomic studies. Hence, the significance of this pathway for production of RP was assessed by identifying its own proteins that were associated to changes in RP production, through subcellular fractionation coupled to shot-gun proteomics. Two CHO cell lines producing a monoclonal antibody with different specific productivities were used as cellular models, from which 4952 protein groups were identified, which represent a coverage of 59% of the Chinese hamster proteome. Data are available via ProteomeXchange with identifier PXD021014. By using SAM and ROTS algorithms, 493 proteins were classified as differentially expressed, of which about 80% was proposed as novel targets and one-third were assigned to the CSP. Endoplasmic reticulum (ER) stress, unfolded protein response, calcium homeostasis, vesicle traffic, glycosylation, autophagy, proteasomal activity, protein synthesis and translocation into ER lumen, and secretion of extracellular matrix components were some of the affected processes that occurred in the secretory pathway. Processes from other cellular compartments, such as DNA replication, transcription, cytoskeleton organization, signaling, and metabolism, were also modified. This study gives new insights into the molecular traits of higher producer cells and provides novel targets for development of new sub-lines with improved phenotypes for RP production.

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Shifted Golgi targeting of glycosyltransferases and α-mannosidase IA from giantin to GM130-GRASP65 results in formation of high mannose N -glycans in aggressive prostate cancer cells

Cited by 19 publications

References 39 publications

N-glycomic Profile in Combat Related Post-Traumatic Stress Disorder

N-glycomic Profile in Combat Related Post-Traumatic Stress Disorder

Overexpression of glycosyltransferase 8 domain containing 2 confers ovarian cancer to CDDP resistance by activating FGFR/PI3K signalling axis

Compartmentalized Proteomic Profiling Outlines the Crucial Role of the Classical Secretory Pathway during Recombinant Protein Production in Chinese Hamster Ovary Cells

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