Metabolomics and 13C Labelled Glucose Tracing to Identify Carbon Incorporation into Aberrant Cell Membrane Glycans in Cancer DOI Creative Commons
Alfredo Reyes-Oliveras, Abigail E. Ellis, Ryan D. Sheldon

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 12, 2024

Abstract Cell membrane glycans contribute to immune recognition, signaling, and cellular adhesion migration, altered glycosylation is a feature of cancer cells that contributes progression. The uptake metabolism glucose other nutrients essential for glycan synthesis could underlie glycosylation, but the relationship between shifts in nutrient effects on have not been directly examined. To address this possibility, we created novel method combines stable isotope tracing with metabolomics enable direct observations allocation nucleotide sugars cell-membrane glycans. We compared two pancreatic cell lines are genetically identical differing energy requirements. 8988-S had higher intracellular pathways relating synthesis, 8988-T commitment non-glycosylation pathways. differed requirements production, resulting differences bioavailability synthesis. workflow demonstrated here enables studies metabolic media results support flux-based regulation mode control functions such migration.

Language: Английский

ST6GAL1‐mediated aberrant sialylation promotes prostate cancer progression DOI Creative Commons
Emma Scott,

Emily Archer Goode,

Rebecca Garnham

et al.

The Journal of Pathology, Journal Year: 2023, Volume and Issue: 261(1), P. 71 - 84

Published: Aug. 7, 2023

Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every type. A common change tumour cell an increase α2,6 sialylation N-glycans, modification driven by the sialyltransferase ST6GAL1. ST6GAL1 overexpressed numerous types, sialylated are fundamental for growth, metastasis, immune evasion, drug resistance, but role prostate poorly understood. Here, we analyse matched normal tissue samples from 200 patients verify that upregulated tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), identify larger branched N-glycans show specificity to We also monitored plasma >400 reveal levels significantly increased blood men with cancer. both vitro vivo studies, demonstrate promotes growth invasion. Our findings introduces on cells raise possibility can secrete active enzyme capable remodelling surface other cells. Furthermore, find expressed be targeted using inhibitor P-3FAX -Neu5Ac. study identifies important progression highlights opportunity inhibit abnormal development new therapeutics. © 2023 The Authors. Journal Pathology published John Wiley & Sons Ltd behalf Pathological Society Great Britain Ireland.

Language: Английский

Citations

25
Sialic acid blockade inhibits the metastatic spread of prostate cancer to bone DOI
Kirsty Hodgson, Margarita Orozco‐Moreno,

Emily Archer Goode

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 104, P. 105163 - 105163

Published: May 20, 2024

Language: Английский

Citations

15
Bioorthogonal Chemical Labeling Probes Targeting Sialic Acid Isomers for N-Glycan MALDI Imaging Mass Spectrometry of Tissues, Cells, and Biofluids DOI Creative Commons
Xiaowei Lu, Colin T. McDowell, Calvin R.K. Blaschke

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(19), P. 7475 - 7486

Published: May 1, 2023

Sialic acid isomers attached in either α2,3 or α2,6 linkage to glycan termini confer distinct chemical, biological, and pathological properties, but they cannot be distinguished by mass differences traditional spectrometry experiments. Multiple derivatization strategies have been developed stabilize facilitate the analysis of sialic their glycoconjugate carriers high-performance liquid chromatography, capillary electrophoresis, workflows. Herein, a set novel schemes are described that result introduction bioorthogonal click chemistry alkyne azide groups into α2,3- α2,8-linked acids. These chemical modifications were validated structurally characterized using model isomeric conjugates protein carriers. Use an alkyne-amine, propargylamine, as second amidation reagent effectively introduces functional group α2,3-linked glycoproteins. In tissues, serum, cultured cells, this allows for detection visualization N-linked imaging approaches. Formalin-fixed paraffin-embedded prostate cancer tissues pancreatic cell lines used characterize numbers distribution alkyne-modified N-glycans. An azide-amine compound with poly(ethylene glycol) linker was evaluated use histochemical staining. amidated amine, reacted biotin-alkyne copper catalyst, detected streptavidin-peroxidase The direct reagents acid-containing glycans glycoproteins provides new glycomic tool expand approaches detection, labeling, visualization, enrichment.

Language: Английский

Citations

20
Sialylated glycoproteins and sialyltransferases in digestive cancers: Mechanisms, diagnostic biomarkers, and therapeutic targets DOI
Shaoze Zhang, A J Lobo, Peifeng Li

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 197, P. 104330 - 104330

Published: March 30, 2024

Language: Английский

Citations

6
The vertebrate sialylation machinery: structure-function and molecular evolution of GT-29 sialyltransferases DOI Creative Commons
Anne Harduin‐Lepers

Glycoconjugate Journal, Journal Year: 2023, Volume and Issue: 40(4), P. 473 - 492

Published: May 29, 2023

Abstract Every eukaryotic cell is covered with a thick layer of complex carbohydrates essential roles in their social life. In Deuterostoma, sialic acids present at the outermost positions glycans glycoconjugates are known to be key players cellular interactions including host-pathogen interactions. Their negative charge and hydrophilic properties enable various normal pathological states expression altered many diseases cancers. Sialylation glycoproteins glycolipids orchestrated by regulated twenty sialyltransferases human tissues distinct enzymatic characteristics preferences for substrates linkages formed. However, still very little on functional organization Golgi apparatus how sialylation machinery finely provide ad hoc sialome cell. This review summarizes current knowledge sialyltransferases, structure–function relationships, molecular evolution, implications biology.

Language: Английский

Citations

15
Sialylation of EGFR by ST6GAL1 induces receptor activation and modulates trafficking dynamics DOI Creative Commons

Katherine E. Ankenbauer,

Tejeshwar C. Rao, Alexa L. Mattheyses

et al.

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(10), P. 105217 - 105217

Published: Sept. 1, 2023

Aberrant glycosylation is a hallmark of cancer cell. One prevalent alteration an enrichment in α2,6-linked sialylation N-glycosylated proteins, modification directed by the ST6GAL1 sialyltransferase. upregulated many malignancies including ovarian cancer. Prior studies have shown that addition α2,6 sialic acid to epidermal growth factor receptor (EGFR) activates this receptor, although mechanism was largely unknown. To investigate role EGFR activation, overexpressed OV4 line, which lacks endogenous ST6GAL1, or knocked-down OVCAR-3 and OVCAR-5 lines, robust expression. Cells with high expression displayed increased activation its downstream signaling targets, AKT NFκB. Using biochemical microscopy approaches, total internal reflection fluorescence microscopy, we determined promoted dimerization higher order oligomerization. Additionally, activity found modulate trafficking dynamics following EGF-induced activation. Specifically, enhanced recycling cell surface while simultaneously inhibiting lysosomal degradation. 3D widefield deconvolution confirmed cells expression, exhibited greater colocalization Rab11 endosomes reduced LAMP1-positive lysosomes. Collectively, our findings highlight novel promotes facilitating oligomerization recycling.

Language: Английский

Citations

15
Sialylation: A Cloak for Tumors to Trick the Immune System in the Microenvironment DOI Creative Commons
Xiaoman Zhou,

Kaijun Chi,

Chairui Zhang

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(6), P. 832 - 832

Published: June 8, 2023

The tumor microenvironment (TME), where the cells incite surrounding normal to create an immune suppressive environment, reduces effectiveness of responses during cancer development. Sialylation, a type glycosylation that occurs on cell surface proteins, lipids, and glycoRNAs, is known accumulate in tumors acts as "cloak" help evade immunological surveillance. In last few years, role sialylation proliferation metastasis has become increasingly evident. With advent single-cell spatial sequencing technologies, more research being conducted understand effects immunity regulation. This review provides updated insights into recent function biology summarizes latest developments sialylation-targeted therapeutics, including antibody-mediated metabolic-based inhibition, well interference with sialic acid-Siglec interaction.

Language: Английский

Citations

14
Sialic acid in the regulation of blood cell production, differentiation and turnover DOI Creative Commons
E. E. Irons, Sajina GC, Joseph T.Y. Lau

et al.

Immunology, Journal Year: 2024, Volume and Issue: 172(4), P. 517 - 532

Published: March 19, 2024

Sialic acid is a unique sugar moiety that resides in the distal and most accessible position of glycans on mammalian cell surface extracellular glycoproteins glycolipids. The potential for sialic to obscure underlying structures has long been postulated, but means by which such structural changes directly affect biological processes continues be elucidated. Here, we appraise growing body literature detailing importance generation, differentiation, function death haematopoietic cells. We conclude sialylation critical post-translational modification utilized haematopoiesis meet dynamic needs organism enforcing rapid availability lineage-specific types. Though thought generated only cell-autonomously within intracellular ER-Golgi secretory apparatus, emerging data also demonstrate previously unexpected diversity mechanisms sialylation. Emphasis afforded mechanism extrinsic sialylation, whereby enzymes remodel glycans, supported charged donor molecules from activated platelets.

Language: Английский

Citations

4
Regulation of PD-L1 glycosylation and advances in cancer immunotherapy DOI
Te-An Lee, En-Yun Tsai, Shou-Hou Liu

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217498 - 217498

Published: Jan. 1, 2025

Language: Английский

Citations

0
Optimizing ST6GAL1 inhibition and selectivity using lithocholic acid-amino acid conjugates for antimetastatic and antiangiogenic agent development DOI
Wei‐Sheng Chen, Christian Angelo P. Concio,

Tzu‐Ting Chang

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108401 - 108401

Published: March 1, 2025

Language: Английский

Citations

0