bims-supasi 2026-10-25 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2026–10–25
twelve papers selected by
Jonathan Wolf Mueller, University of Birmingham

Redox-Controlled Site-Specific O-Sulfation Facilitated Diversity-Oriented Chemoenzymatic Synthesis of Chondroitin Sulfates A/C/E and Chimeric Chondroitin Sulfates.
A phenylboronic acid-modified gelatin/oxidized chondroitin sulfate hydrogel with reversible adhesion and self-healing properties for enhanced chronic wound treatment.
Programmable chemoenzymatic synthesis of a keratan sulfate N-glycan library for glycocode decoding.
Systematic Virtual Screening of Heparan Sulfate Oligosaccharides and Mechanistic Insights into Heparanase Inhibition.
Structural complexity and biofunctional properties of highly sulfated carrageenan-agaroid galactans from Calliblepharis fimbriata: Insights from selective chemical modifications.
Mapping of pikachurin heparan sulfate modification to a region dispensable for synaptic localization in photoreceptors.
Sulfate Groups Modulate the Protective Effects of Laminaria japonica Fucoidan against High-Fat Diet-Induced Intestinal Mucus Layer Injury via Gut Microbiota Regulation and Metabolic Profiling.
Potential to modulate corneal epithelial repair via nitric oxide-releasing glycosaminoglycans.
A Theranostic Nanozyme for Osteoarthritis Treatment and Glycosaminoglycan-Targeted Diagnosis of Cartilage Pathology.
Comprehensive behavioral phenotyping of male Sulf1-deficient mice reveals reduced locomotor activity, altered forelimb gait, and reduced prepulse inhibition.
Age-specific associations of estrone sulfate, DHEAS, and anti-Müllerian hormone with depressive symptom dimensions in men.
Aggregation of Mutant p53 Alters Sialylated and Sulfated Glycan Profiles and Enhances Siglec-9 Ligand Availability in Ovarian Cancer.

Org Lett. 2026 Oct 16. 28(41): 13052-13057

Redox-Controlled Site-Specific O-Sulfation Facilitated Diversity-Oriented Chemoenzymatic Synthesis of Chondroitin Sulfates A/C/E and Chimeric Chondroitin Sulfates.

Yan Zhang, Zhilin Zhang, Mengru Niu, Yaqi Wang, Kan Zhong, Haiyang Wu, Jinfeng Ye, Zhifei Hu, Saddam M Muthana, Hongzhi Cao.

The biological functions of chondroitin sulfate (CS) are strongly influenced by its sulfation pattern. However, the limited site selectivity of currently available sulfotransferases has made it challenging to access CS oligosaccharides with diverse sulfation patterns. Herein, we report a redox-controlled site-specific O-sulfation strategy for the programmable installation of CS-A, CS-C, or CS-E sequences at defined positions along chondroitin backbones, enabling the diversity-oriented synthesis of 28 structurally well-defined CS oligosaccharides with distinct sulfation sequences.

DOI: https://doi.org/10.1021/acs.orglett.6c03858
Int J Biol Macromol. 2026 Oct 20. pii: S0141-8130(26)04919-6. [Epub ahead of print] 154967

A phenylboronic acid-modified gelatin/oxidized chondroitin sulfate hydrogel with reversible adhesion and self-healing properties for enhanced chronic wound treatment.

Hongning Qu, Zhuofan Dong, Jiaxin Han, Zekun Su, Shaohan Zhang, Yian Zhao, Xufeng Dong, Junwei Zong.

  Chronic wounds are a major clinical challenge, commonly associated with diabetes, vascular diseases, and prolonged immobilization. Their varying depths and irregular geometries require wound dressings that can conform closely to complex wound surfaces while maintaining reliable adhesion. Although adhesive and dynamic hydrogels have been widely explored for wound management, integrating stable adhesion during application with controllable and gentle on-demand detachment, while retaining self-healing and injectability for irregular chronic wounds, remains challenging. Therefore, this study aimed to develop an adaptive hydrogel dressing capable of conforming to irregular chronic wounds while providing stable adhesion during application and controllable, gentle detachment on demand. To achieve this aim, we developed a temperature-responsive phenylboronic acid-modified gelatin/oxidized chondroitin sulfate (GP-OCS) hydrogel, integrating Schiff base and borate ester bonds formed between phenylboronic acid-modified gelatin and oxidized chondroitin sulfate. The resulting dual dynamic network endowed the hydrogel with favorable mechanical properties, self-healing ability, injectability, and temperature-responsive reversible adhesion, enabling close conformity to irregular wound surfaces and on-demand removal. These findings demonstrate a dual-dynamic-covalent hydrogel strategy that combines conformability, stable adhesion, and temperature-triggered atraumatic removal, providing a promising approach for the development of adaptive wound dressings for chronic wound management.

Keywords:  Reversible adhesion; Self-healing; Temperature-response

DOI:  https://doi.org/10.1016/j.ijbiomac.2026.154967
Proc Natl Acad Sci U S A. 2026 Oct 27. 123(43): e2621414123

Programmable chemoenzymatic synthesis of a keratan sulfate N-glycan library for glycocode decoding.

Kaixuan Wang, Wenjing Ma, Wei Zhang, Tianhui Hao, Mengjia Zhang, Wentao Li, Wei Zhao, Zhuojia Xu, Tiehai Li.

  Keratan sulfate (KS) is a unique and widely distributed glycosaminoglycans family implicated in diverse biological processes. KS features branched glycan architectures with diverse sialylation and sulfation patterns, encoding a vastly expanded chemical and biological space. The limited accessibility of well-defined structures has hindered precise investigations into the KS biological functions. Here we report a programmable chemoenzymatic platform for assembling a 106-membered library of KS N-glycans and their nonsulfated counterparts, featuring length-variable oligo-N-acetyllactosamine (LacNAc) extensions and encompassing diverse sulfation and sialylation patterns. The synthetic strategy integrates length-controlled iterative glycosylation to assemble versatile precursors, orthogonal deprotection for site-specific sulfation, and modular enzyme-driven diversification. Glycan microarray analysis of this comprehensive library reveals that glycan-protein recognition is governed by the interplay of sulfation and sialylation patterns, oligo-LacNAc chain length, and terminal epitope presentation, providing insight into the functional versatility of KS glycans.

Keywords:  N-glycan; biomolecular recognition; carbohydrates; chemoenzymatic synthesis; keratan sulfate

DOI:  https://doi.org/10.1073/pnas.2621414123
ACS Chem Biol. 2026 Sep 18. 21(9): 2286-2297

Systematic Virtual Screening of Heparan Sulfate Oligosaccharides and Mechanistic Insights into Heparanase Inhibition.

Binjie Li, Siran Zhao, Zonglin Lan, Marco Maccarana, Xiao Zhang, Vito Ferro, Hui Cao, Tianji Zhang, Mingjia Yu, Jin-Ping Li.

Heparanase (Hpse) is an endo-β-glucuronidase that specifically cleaves heparan sulfate (HS) and plays critical roles in the pathogenesis of multiple diseases, making it a well-validated therapeutic target. To identify novel Hpse inhibitors, we developed a rule-based computational pipeline to construct a rigorously curated database of HS oligosaccharides ranging from disaccharides to hexasaccharides. This database systematically encompasses all possible sulfation patterns and stereochemical configurations of the three monosaccharide species in HS. Using a multistage virtual screening strategy against Hpse, we prioritized high-affinity HS oligosaccharides for detailed analysis. Structural motif profiling of the top-ranking candidates revealed that even-numbered oligosaccharides preferentially retain the iduronic acid (IdoA)-N-acetyl-3-O-sulfated glucosamine (GlcNAc3S) motif, whereas odd-numbered species are enriched with IdoA2S and 3,6-O-sulfated glucosamine (GlcN3S6S) motifs. Systematic desulfation of the lead compound, HP-dp5R1, found that removal of 2-O- or 3-O-sulfate groups resulted in substantially larger penalties to binding-free energy compared with removal of 6-O- or N-sulfates, indicating a dominant role for 2-O/3-O sulfation in Hpse recognition. Molecular dynamics simulations and binding-free energy calculations further revealed that longer oligosaccharides form extensive interactions with the heparin-binding domains (HBD1 and HBD2) flanking the catalytic cleft, leading to reduced conformational fluctuation. Together with preliminary experimental results using selected octasaccharides that resemble the structural features of the top-hit oligosaccharides identified from virtual screening, we demonstrate that the integrated computational platform provides a robust foundation for the rational design of HS-based Hpse inhibitors. More broadly, the virtual HS oligosaccharide database described here is expected to serve as a powerful resource for screening other HS-binding proteins and for the discovery of novel agonists or antagonists.

DOI: https://doi.org/10.1021/acschembio.6c00454
Carbohydr Polym. 2026 Nov 15. pii: S0144-8617(26)00983-5. [Epub ahead of print]392 125866

Structural complexity and biofunctional properties of highly sulfated carrageenan-agaroid galactans from Calliblepharis fimbriata: Insights from selective chemical modifications.

Clarisa Naa Shormeh Darko, Sanjida Humayun, Vitalijs Rjabovs, Neill J Goosen, Rando Tuvikene.

  Galactans isolated from Calliblepharis fimbriata were characterized using selective chemical modification approaches coupled with 1D and 2D NMR spectroscopy to elucidate their structural complexity and structure-activity relationships. The polysaccharides comprised mixed d and l-galactopyranosyl residues associated with ι-carrageenan (G4S - DA2S) and porphyran (G - L6S) motifs. 1H13C HSQC analysis of chemically desulfated derivatives revealed preferential removal of sulfate groups at C-4, while DA2S and L6S units remained largely preserved, yielding α-carrageenan (G - DA2S) segments. Alkali treatment induced partial cyclization of precursor residues, and the principal fraction exhibited a molar ratio of d-galactose, 3,6-anhydrogalactose, and sulfate ester of 1.00:0.04:0.36. Structure-activity relationship analysis suggested that sulfate substitution at C-2 and C-4 positions contributed to an enhanced anticoagulant activity, and high anionic moieties were further associated with increased inhibition of α-glucosidase (38.2-68.8%) and α-amylase (15.3-86%). Furthermore, the galactans exhibited non-cytotoxicity toward RAW264.7 macrophages at concentrations below 32 μg/mL and significantly enhanced (p < 0.05) phagocytic activity and nitric oxide production in a concentration-dependent manner, indicating an immunostimulatory potential through macrophage activation. Overall, these findings reveal the structural complexity of C. fimbriata galactans and establish clear links between their distinct sulfation patterns and biological functions, providing a basis for their potential biomedical and nutraceutical applications.

Keywords:  Alkaline treatment; Anticoagulation; Chemical desulfation; Hybrid galactans; RAW264.7 macrophages; α-Amylase

DOI:  https://doi.org/10.1016/j.carbpol.2026.125866
J Biol Chem. 2026 Oct 21. pii: S0021-9258(26)02504-4. [Epub ahead of print] 113632

Mapping of pikachurin heparan sulfate modification to a region dispensable for synaptic localization in photoreceptors.

Robyn V McGowan, Faiyaz A K Abid, Melina A Agosto.

Rod and cone photoreceptors (PRs) are specialized neurons that detect light, then transmit information to bipolar cells at synapses in the outer plexiform layer of the retina. Pikachurin (PIKA) is a multi-domain heparan sulfate (HS) proteoglycan expressed in PRs. It is secreted into the synaptic cleft, where it binds to presynaptic dystroglycan, postsynaptic orphan receptor GPR179, and postsynaptic adhesion molecule LRRTM4. Knockout of PIKA results in ultrastructural and functional defects at rod synapses. However, the role of HS in PIKA function at synapses is unknown. Using a panel of deletion and truncation mutants expressed in heterologous cells, we determined that a.a. 240-342, a region of unknown function between the last fibronectin III domain and the first EGF-like domain, is necessary and sufficient for PIKA HS modification. Site-directed mutagenesis of S244, identified as a likely candidate based on neighboring sequences, abolished HS modification, indicating that this residue is the sole HS attachment site. Deletion of the 240-342 region or mutation of S244 also abolished co-immunoprecipitation of LRRTM4, consistent with the previously reported HS-dependent binding. To assess requirements for synaptic localization, PIKA mutants were expressed in mouse rods. Deletion of the HS-containing region or the fibronectin III domains did not prevent localization at rod presynapses. In contrast, deletion of the first EGF-like and laminin G domains severely impaired localization, suggesting an important role for these domains in mediating trafficking or synaptic enrichment.

DOI: https://doi.org/10.1016/j.jbc.2026.113632
J Agric Food Chem. 2026 Oct 07. 74(39): 30845-30858

Sulfate Groups Modulate the Protective Effects of Laminaria japonica Fucoidan against High-Fat Diet-Induced Intestinal Mucus Layer Injury via Gut Microbiota Regulation and Metabolic Profiling.

Huiru Li, Jin Chen, Chuqiao Zhang, Wanshuang Cai, Hongxia Che, Hongyan Li.

  Sulfate groups are key to fucoidan's protection against intestinal mucus barrier damage, but their exact mechanisms remain unclear. This study compared native fucoidan (Fud, sulfate content 26.6%) and desulfated fucoidan (dsFud, sulfate content 2.2%) in a high-fat diet-induced colonic mucus-layer injury mouse model. Both interventions mitigated weight gain, fat accumulation, and dyslipidemia, increased the neutral/acidic mucin ratio and upregulated Muc2 expression, and alleviated colon inflammation as well as NLRP3 inflammasome activation. Compared with dsFud, Fud showed better hepatic lipid regulation and serum triglyceride reduction, upregulated Fut2 more significantly, and more potently inhibited NLRP3 signaling. Fud also markedly reduced the Firmicutes/Bacteroidota ratio and enriched Parabacteroides, Desulfovibrio, and Akkermansia. Metabolomic profiling revealed that they both suppressed primary bile acid metabolism and activated the aryl hydrocarbon receptor. Notably, Fud activated tryptophan metabolism, while dsFud mainly enhanced arginine and proline metabolism. Collectively, sulfation is important for fucoidan's protective potency on the intestinal mucus layer.

Keywords:  Colonic mucus layer; Desulfated fucoidan; Gut microbiota; Metabolomics; Sulfated fucoidan

DOI:  https://doi.org/10.1021/acs.jafc.6c08201
RSC Pharm. 2026 Oct 09.

Potential to modulate corneal epithelial repair via nitric oxide-releasing glycosaminoglycans.

Margery E Purvis, Madelyn P Bucci, Tsian D Ramrattan, Shannon M Wallet, Mark H Schoenfisch.

Bioactive wound therapies that protect injured tissue, promote regeneration, and prevent infection would represent a promising alternative to traditional passive treatments. In this study, nitric oxide (NO)-releasing glycosaminoglycans (GAGs) were synthesized and evaluated for their therapeutic potential in corneal wound healing. Low and high molecular weight hyaluronic acid (HA) and chondroitin sulfate (CS) derivatives of different sulfation patterns were synthesized and characterized with respect to NO release, antibacterial activity, cytotoxicity, and effects on human corneal epithelial cell proliferation and migration. A three-dimensional corneal tissue scratch closure model was subsequently used to assess in vitro barrier restoration. A derivative consisting of CS with prolonged NO release and low molecular weight HA with intermediate NO-release kinetics were identified as the most promising materials. The HA derivative enhanced epithelial migration even during later timepoints of the migration assays. A carboxymethylcellulose (CMC) gel formulation containing the HA derivative further promoted cell migration. In corneal tissue models, treatment with both the free and CMC-formulated NO-releasing HA enhanced restoration. Barrier recovery, as measured by transepithelial electrical resistance, confirmed restoration of tissue integrity post-wounding, concomitant with a cytokine milieu associated with pro-wound healing. Overall, NO-releasing, low molecular weight HA in a CMC gel formulation represents a promising bioactive strategy for promoting corneal wound repair.

DOI: https://doi.org/10.1039/d6pm00190d
ACS Nano. 2026 Sep 22. 20(37): 25841-25858

A Theranostic Nanozyme for Osteoarthritis Treatment and Glycosaminoglycan-Targeted Diagnosis of Cartilage Pathology.

Dongze Mo, Yanbing Wen, Chaoqun Cheng, Xiwen Chen, Qi Sun, Hanjie Zhang, Xueying An, Wanling Liu, Xiaomiao Cui, Yihong Zhang, Quan Wang, Chenxin Zhu, Jiawei Li, Hao Dong, Hui Wei.

  The lack of vascular and neural innervations in cartilage often results in poor drug delivery and penetration, compromising the efficacy of current therapeutics. To tackle this clinical challenge, we designed positively charged manganese-doped CeO2 nanozymes that combine reactive oxygen species (ROS)-scavenging activity with prolonged retention in the joint cavity by taking advantage of the negatively charged cartilage matrix. Integrating coarse-grained molecular dynamics simulations with experimental validation, we identified chondroitin sulfate as the key glycosaminoglycan responsible for mediating the retention of these positively charged nanozymes in the joint cavity. After intra-articular administration, manganese-doped CeO2 promoted cartilage defect repair and subchondral bone remodeling in a rat model within 4 weeks. In addition, benefiting from the multiple enzyme mimicking activity of nanozymes, the peroxidase-like activity of manganese-doped CeO2 was explored to develop a pathological assay to detect the state of cartilage repair. This study establishes an integrated framework combining theoretical modeling with experimental validation to elucidate intra-articular retention mechanisms. The framework enables the rational design of theranostic nanozymes that exploit disease-specific pathological features for both diagnosis and therapy.

Keywords:  cartilage; molecular dynamics; nanozymes; osteoarthritis; pathology diagnosis

DOI:  https://doi.org/10.1021/acsnano.6c15540
Mol Brain. 2026 Oct 17. pii: 73. [Epub ahead of print]19(1):

Comprehensive behavioral phenotyping of male Sulf1-deficient mice reveals reduced locomotor activity, altered forelimb gait, and reduced prepulse inhibition.

Kazuko Keino-Masu, Markos Michail Chatzigiannis, Hirotaka Shoji, Nobuyuki Yamasaki, Takuya Okada, Yasue Horiuchi, Tadao Arinami, Yoko Hagino, Kazutaka Ikeda, Tsuyoshi Miyakawa, Masayuki Masu.

  Sulfatase 1 (Sulf1) is an extracellular sulfatase that regulates multiple signaling pathways by removing 6-O-sulfate from heparan sulfate. Although Sulf1 has established roles in development and cancer, its functions in the adult brain remain incompletely characterized. Recently we reported that Sulf1 is expressed in the nucleus accumbens, overlapping with dopamine D1 and D2 receptors, and that Sulf1 knockout (KO) mice showed altered reward and aversion learning. However, given that Sulf1 is expressed in many other brain regions, including the prefrontal cortex, midline thalamic nuclei, etc., Sulf1 may have unknown brain functions. To explore the Sulf1 functions across a broad range of contexts, we here perform a comprehensive behavioral analysis of male Sulf1 KO mice, together with a re-analysis of the original data in which the false discovery rate (FDR) was controlled within defined groups of tests. Sulf1 KO mice traveled less than wild-type (WT) mice in the open field test, and this reduction was reproduced in an independent cohort. Gait analysis on a treadmill revealed a redistribution of the forelimb stance phase, with a larger proportion spent braking and a smaller proportion spent propelling, together with an increased absolute paw angle; these forelimb changes were reproduced in 2 independent cohorts and at 2 treadmill speeds. Distance traveled was also reduced in a three-chamber apparatus and, before drug injection, at nominal significance in the home cage. Sulf1 KO mice showed larger acoustic startle responses and reduced prepulse inhibition (PPI); the reduction in PPI was observed in all 5 drug-free or saline-treated sessions conducted in 2 independent cohorts and was also observed after haloperidol (0.3 or 1 mg/kg) and, at nominal significance, after clozapine (3 mg/kg) treatment. The locomotor, vertical, and stereotypic responses to methamphetamine were attenuated in Sulf1 KO mice, with nominally significant drug × genotype interactions. Increased baseline-subtracted contextual freezing provides a promising lead for further confirmation. Taken together, adult male Sulf1 KO mice exhibit alterations in locomotor output, forelimb gait, and sensorimotor gating, implicating that Sulf1 deficiency leads to a wide range of neurobehavioral abnormalities.

Keywords:  Behavioral test battery; Gait analysis; Knockout mouse; Open field test; Prepulse inhibition; Sulfatase 1 (Sulf1)

DOI:  https://doi.org/10.1186/s13041-026-01353-8
Psychiatry Res. 2026 Oct 19. pii: S0165-1781(26)00599-8. [Epub ahead of print]367 117540

Age-specific associations of estrone sulfate, DHEAS, and anti-Müllerian hormone with depressive symptom dimensions in men.

Xiaoxia Duan, Di Jing, Mingjing Situ, Pei Liu, Yujie Tao, Yi Huang.

   BACKGROUND: Sex hormones influence brain circuits that regulate mood, but previous studies in men have focused on few hormones and treated depression as a single condition. In a nationally representative sample of men, we systematically examine 12 serum sex hormones across the adult lifespan in relation to dimensional depressive symptoms.
METHODS: We analyzed cross-sectional data from the National Health and Nutrition Examination Survey (2017-2023). Serum sex hormones were measured, and depressive symptoms were assessed by PHQ-9, with a score ≥5 indicating mild or greater symptoms. Survey-weighted regression models examined associations between hormones and depressive symptoms, total scores, somatic/non-somatic subscales, and nine individual symptoms.
RESULTS: Among 5668 men (mean age 51.1 years), 1344 (23.7%) had depressive symptoms. Higher anti-Müllerian hormone (AMH, OR=0.86), dehydroepiandrosterone sulfate (DHEAS, OR=0.83), and estrone sulfate (ES1, OR=0.87) were associated with lower odds of depressive symptoms; higher luteinizing hormone (LH, OR=1.11) with increased odds. Age-stratified analyses showed ES1 was inversely associated with depressive symptoms in middle-aged and older men, DHEAS only in older men, and AMH in younger and middle-aged men. Dimensionally, ES1, AMH, and testosterone were associated with lower somatic symptom scores (β=-0.12, -0.16, and -0.17), while AMH was also associated with lower non-somatic scores (β=-0.23). AMH was inversely associated with concentration difficulties; FSH and LH with sleep disturbance.
CONCLUSIONS: Sex hormones show distinct, age and symptom-dimension-specific associations with male depression, challenging unitary diagnostic approaches. These findings support hormone-informed subtyping of male depression and suggest clinical assessment should consider both age and symptom presentation.

Keywords:  Age-specific associations; Anti-Müllerian hormone; Estrone sulfate; Male depression; Symptom dimensions

DOI:  https://doi.org/10.1016/j.psychres.2026.117540
Lab Invest. 2026 Oct 23. pii: S0023-6837(26)00103-0. [Epub ahead of print] 106173

Aggregation of Mutant p53 Alters Sialylated and Sulfated Glycan Profiles and Enhances Siglec-9 Ligand Availability in Ovarian Cancer.

Midori Ikezaki, Noa Mori, Yoshiko Takeda-Uchimura, Naoyuki Iwahashi, Megumi Fujino, Kaho Nishioka, Kazuhiko Ino, Yoshito Ihara, Masakazu Fujimoto, Yukio Fujiwara, Yoshihiro Komohara, Kenji Uchimura, Kazuchika Nishitsuji.

   PURPOSE: Mutant p53 proteins form aggregates, and the presence of such cytoplasmic p53 aggregates has predicted poor prognosis in several cancers including high-grade serous ovarian cancer (HGSOC). The existence of aberrant expressions of sialylated and sulfated glycans is a major feature of various cancers. At present, the correlation between the presence of cytoplasmic p53 aggregates and the existence of aberrant glycosylation in cancers is unclear. Here, we investigated whether the presence of p53 aggregates may affect sialylated and sulfated glycan profiles in HGSOC.
MATERIALS AND METHODS: We used the CL40 monoclonal antibody that recognizes sialyl 6-sulfo Lewis X and sialyl 6-sulfo N-acetyllactosamine and a cell-permeable p53 aggregation inhibitor ReACp53. HGSOC tissues were examined by immunohistochemistry with CL40. Expressions of GlcNAc-6-O-sulfotransferases (GlcNAc6STs) in HGSOC-derived OVCAR-3 cells were analyzed by means of semi-quantitative PCR. Binding of sialic acid-binding immunoglobulin-like lectin Siglec-9 to OVCAR-3 cells were analyzed by using His-tagged Siglec-9.
RESULTS: OVCAR-3 cells expressed CL40-reactive glycans, but CL40 reactivity was reduced by p53 disaggregation. Immunohistochemical analyses revealed expression of CL40-reactive glycans in p53 aggregate-positive HGSOC cases. Recognition of glycans by CL40 requires 6-O-sulfation of the N-acetylglucosamine (GlcNAc) residues, which are catalyzed by GlcNAc6STs. mRNA expressions of GlcNAc6ST2/CHST4, GlcNAc6ST3/CHST5, and GlcNAc6ST5/CHST6 were down-regulated in the presence of ReACp53. Pretreatment of OVCAR-3 cells with CL40 prevented the binding of Siglec-9 and OVCAR-3 cells, which suggested that CL40 epitopes could be recognized by the Siglec-9 lectin.
CONCLUSIONS: Our results together suggest a novel mechanism of aberrant glycosylation in HGSOC associated with p53 aggregation.

Keywords:  GlcNAc-6-O-sulfotransferase; Siglec; high-grade serous ovarian carcinoma; p53; p53 aggregates; sulfated glycan

DOI:  https://doi.org/10.1016/j.labinv.2026.106173