Transcriptional Regulation of the Protocadherin β Cluster during Her-2 Protein-induced Mammary Tumorigenesis Results from Altered N-Glycan Branching

Guo, Hua-Bei; Nairn, Alison V.; Rosa, Mitche dela; Nagy, Tamás; Zhao, Shaying; Moremen, Kelley W.; Pierce, Michael

doi:10.1074/jbc.m112.369355

Cited by 20 publications

(13 citation statements)

References 56 publications

(78 reference statements)

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“…In contrast, neither of these reported pathways was associated with TRIM44. Interestingly, microarray analysis showed that nine out of top 20 downregulated genes had oncogenic function ( C3AR1, FMN1, GBP1, ST3GAL5, NT5E, RAB27B, FBP2, HIPK3, PLAU , and 8 out of 20 top up‐regulated genes had tumor suppressive function ( NUPR1, CDK19, CADM1, INHBA, TNFSF10, PRKACB, PCDHB6, DDIT4 ). Furthermore, six of these eight tumor suppressive genes are associated with apoptotic mechanisms ( NUPR1 , CDK19, CADM1, INHBA, TNFSF10, DDIT4 ).…”

Section: Discussionmentioning

confidence: 99%

A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor

et al. 2016

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Tripartite motif 44 (TRIM44) is one of the TRIM family proteins that are involved in ubiquitination and degradation of target proteins by modulating E3 ubiquitin ligases. TRIM44 overexpression has been observed in various cancers. However, its association with testicular germ cell tumor (TGCT) is unknown. We aimed to investigate the clinical significance of TRIM44 and its function in TGCT. High expression of TRIM44 was significantly associated with α feto‐protein levels, clinical stage, nonseminomatous germ cell tumor (NSGCT), and cancer‐specific survival (P = 0.0009, P = 0.0035, P = 0.0004, and P = 0.0140, respectively). Multivariate analysis showed that positive TRIM44 IR was an independent predictor of cancer‐specific mortality (P = 0.046). Gain‐of‐function study revealed that overexpression of TRIM44 promoted cell proliferation and migration of NTERA2 and NEC8 cells. Knockdown of TRIM44 using siRNA promoted apoptosis and repressed cell proliferation and migration in these cells. Microarray analysis of NTERA2 cells revealed that tumor suppressor genes such as CADM1,CDK19, and PRKACB were upregulated in TRIM44‐knockdown cells compared to control cells. In contrast, oncogenic genes including C3AR1,ST3GAL5, and NT5E were downregulated in those cells. These results suggest that high expression of TRIM44 is associated with poor prognosis and that TRIM44 plays significant role in cell proliferation, migration, and anti‐apoptosis in TGCT.

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Section: Discussionmentioning

confidence: 99%

A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor

et al. 2016

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“…The galectin interaction with branched N-glycans on integrins is associated with turnover and maturation of the FA, fibronectin fibrillogensis and actin microfilament remodelling (12,27). Knockdown of MGAT5 in cancer cells has been shown to reduce N-glycan branched on N-CAD and turnover of cell-cell adhesions, as well as cell migration (32). Removal of three sites with branched Nglycans from N-CAD did not alter surface expression but did reduced cancer cell migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

Glioma stem cells invasive phenotype at optimal stiffness is driven by MGAT5 dependent mechanosensing

Marhuenda

Fabre

Zhang

et al. 2020

Preprint

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Glioblastomas stem-like cells (GSCs) by invading the brain parenchyma escape resection and radiotherapy. GSC invasion is associated with altered N-glycosylation pattern of integrins and other transmembrane proteins resulting in changed mechanosensing but details are elusive. Because the tumour microenvironment has an increased stiffness we studied the interaction between matrix stiffness, N-glycosylation and GSC migration. To mimic the fibrillar microenvironments, we designed 3D-ex-polyacrylonitrile nanofibers scaffolds (NFS) with adjustable stiffnesses by loading multiwall carbon nanotubes (MWCNT). We found that migration of GSCs was maximum at 166 kPa. Migration rate was correlated with cell shape, expression of focal adhesion (FA), Epithelial to Mesenchymal Transition (EMT) proteins and (β1,6) branched N-glycan binding, galectin-3. Mutation of MGAT5 in GSC inhibited N-glycans (β1–6) branching, suppressed the stiffness dependence of FA and EMT protein expression as well as migration on 166kPa NFS; underpinning the role of multibranched N-glycans as a critical regulator of mechanotransduction by GSC.Significance StatementDuring pathological processes in which cell migration is involved, cells undergo important functional changes in protein glycosylation and are responsive to environmental mechanical modifications. We addressed the question of the glycosylation role in mechanotransduction regulation of glioma stem cells. We created a bio-inspired 3D nanofiber scaffold (NFS) loaded with multiwall carbon nanotubes to obtain NFS of adjustable stiffness in physiological and pathological ranges. We highlighted and described a mechanism of fine mechanotransduction leading to a nonlinear migration response regarding to 3D microenvironment stiffness values. We show the importance to develop mechano-pharmacology as new therapeutic target by demonstrating the relationship existing between environmental stiffness and multibranched N-glycans catalysed by the MGAT5 enzyme to optimize directed migration.

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“…However, the epitope for these antibodies were mostly designed against the protein moiety and not towards the N ‐glycan structures . To date, N ‐glycan based biomarkers or models have been developed to help validate diagnosis and evaluate outcomes for various cancers or other illnesses, including liver cancer , rectal carcinoma , ovarian cancer and lung cancer . Some reviews have highlighted the promising prospect of N ‐glycans as cancer biomarkers and the progress in glycomic research strategies recently .…”

Section: Discussionmentioning

confidence: 99%

“…Serum protein N ‐glycan analysis was performed using DSA‐FACE technology as described previously . Briefly, the N ‐glycans present on glycoproteins in 2 μL of serum were released with peptide N ‐glycosidase‐F (PNGaseF) (New England Biolabs, Boston, MA).…”

Section: Methodsmentioning

confidence: 99%

Serum N‐glycans outperform CA19‐9 in diagnosis of extrahepatic cholangiocarcinoma

et al. 2017

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Extensive efforts have been devoted to improve the diagnosis of extrahepatic cholangiocarcinoma (ECCA) due to its silent clinical character and lack of effective diagnostic biomarkers. Specific alterations in N-glycosylation of glycoproteins are considered a key component in cancer progression, which can serve as a distinct molecular signature for cancer detection. This study aims to find potential serum N-glycan markers for ECCA. In total, 255 serum samples from patients with ECCA (n = 106), benign bile tract disease (BBD, n = 60) and healthy controls (HC, n = 89) were recruited. Only 2 μL of serum from individual patients was used in this assay where the N-glycome of serum glycoproteins was profiled by DNA sequencer-assisted fluorophore-assisted capillary electrophoresis (DSA-FACE) technology. Multi-parameter models were constructed by combining the N-glycans and carbohydrate antigen 19-9 (CA19-9) which is currently used clinically. Quantitative analyses showed that among 13 N-glycan structures, the bifucosylated triantennary N-glycan (peak10, NA3F2) presented the best diagnostic performance for distinguishing ECCA from BBD and HC. Two diagnostic models (Glycotest1 and Glycotest2) performed better than single N-glycan or CA19-9. Additionally, two N-glycan structures (peak9, NA3Fb; peak12, NA4Fb) were tightly related to lymph node metastasis in ECCA patients. In conclusion, sera of ECCA showed relatively specific N-glycome profiling patterns. Serum N-glycan markers and models are novel, valuable and noninvasive alternatives in ECCA diagnosis and progression monitoring.

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Transcriptional Regulation of the Protocadherin β Cluster during Her-2 Protein-induced Mammary Tumorigenesis Results from Altered N-Glycan Branching

Cited by 20 publications

References 56 publications

A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor

A novel prognostic factor TRIM44 promotes cell proliferation and migration, and inhibits apoptosis in testicular germ cell tumor

Glioma stem cells invasive phenotype at optimal stiffness is driven by MGAT5 dependent mechanosensing

Serum N‐glycans outperform CA19‐9 in diagnosis of extrahepatic cholangiocarcinoma

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