ErbB2 Glycomic Data from WT and ST6GAL1 K.O. Gastric Cancer Cells
Ontology highlight
ABSTRACT: Glycomic analysis of total N-glycan species released from ErbB2 isolated from WT and ST6GAL1 K.O. ErbB2-positive gastric cancer cells (NCI-N87)
Project description:To discover potential biomarkers of melanoma development and progression, we embarked on studies comparing the glycomic gene profiles of normal human epidermal melanocytes with human metastatic melanoma (MM) cells represented by A375 and G361 cell lines. Glycomic features embody all of those enzymatic, membranous and regulatory proteins that influence glycan ‘sugar’ formation/degradation on a cell. Comparative expression profiling of glycomic genes indicated that several genes were differentially expressed between normal melanocytes and MM cells. We speculate that glycome genes differentially expressed in MM cells help drive malignant and metastatic behavior of MM cells and could potentially serve as a biomarker(s) of melanoma progression.
Project description:The clinical performance of trastuzumab in the treatment of ErbB2-positive gastric cancer is severely hampered by the emergence of molecular resistance. The glycosylation landscape of ErbB2’s extracellular domain, and the molecular mechanisms through which it tunes gastric cell malignancy, including the acquisition of trastuzumab resistance, remain elusive. We show that the expression of ErbB2 sialylated glycoforms holds clinical utility in the prediction of clinical outcome and stratification of gastric cancer patients. In-depth glycoproteomic and glycomic analysis of ErbB2 extracellular region disclosed a site-specific profile in gastric cancer cells. We further demonstrate that ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites within the trastuzumab binding domain. Moreover, the abrogation of ST6Gal1-mediated α2,6-sialylation reshapes ErbB2 glycome and sensitizes gastric cancer cells to trastuzumab-induced cytotoxicity through receptor membrane stabilization and a downregulation of ErbB2 activation. Overall, this data demonstrates that aberrant sialylation tunes the molecular resistance of ErbB2-driven gastric cancer cells to trastuzumab.
Project description:People with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1,216 women and men, both living with virally suppressed HIV and those without HIV. Our glycan-based machine learning models indicate that living with chronic HIV significantly accelerates the accumulation of pro-aging associated glycomic alterations. Consistently, PWH exhibit heightened expression of senescence associated glycan-degrading enzymes compared to their controls. These glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit reduced anti-HIV IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.
2024-03-21 | PXD046510 | Pride
Project description:Glycomic profiling of the gut microbiota by Glycan-seq
Project description:Gene expression profiling of ErbB2-engineered MCF10A and WT cells in 2D and 3D culture Gene expression profiling of ErbB2-engineered MCF10A and WT cells, 2D and 3D culture, 5 or 6 replicates
Project description:In collaboration with Professor Anne Dell at the South Kensington Campus of Imperial College London, we have conducted preliminary glycomic surveys of C57BL/6 CD25+ and CD25- CD4+ T cells. Cells selected in serum-containing culture medium demonstrated unusual N-glycan profiles compared to those prepared in phosphate buffered saline (PBS). These profiles were subsequently shown to result from cellular sequestration of glycoproteins present in fetal calf serum (FCS) used to supplement the medium (1). Analysis of the N-glycan profile of murine CD4+CD25+ Tregs prepared in PBS revealed distinct differences from CD4+CD25- T cells – namely, a reduction in sialic acid capping and loss of core fucose.
Project description:In collaboration with Professor Anne Dell at the South Kensington Campus of Imperial College London, we have conducted preliminary glycomic surveys of C57BL/6 CD25+ and CD25- CD4+ T cells. Cells selected in serum-containing culture medium demonstrated unusual N-glycan profiles compared to those prepared in phosphate buffered saline (PBS). These profiles were subsequently shown to result from cellular sequestration of glycoproteins present in fetal calf serum (FCS) used to supplement the medium (1). Analysis of the N-glycan profile of murine CD4+CD25+ Tregs prepared in PBS revealed distinct differences from CD4+CD25- T cells – namely, a reduction in sialic acid capping and loss of core fucose.
Project description:Using ChIP-seq, we identified the genome-wide occupancy of SMARCA2 and SMARCA4 in lung cancer cells (NCI-H1944) reconstituted with SMARCA4 WT. We also determined how SMARCA4 occupancy changed in NCI-H1944 after SMARCA2 depletion.
Project description:Using ATAC-seq, we identified the accessibility changes in lung cancer cells (NCI-H1944) reconstituted with SMARCA4 WT or SMARCA4 mutants. We also determined the SMARCA2-regulated accessibility program in NCI-H1944 after SMARCA2 depletion. Lastly, we identified the SMARCA2 accessibility program that is rescued by SMARCA4 WT and mutants. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech.