Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 35(2), P. 88 - 90
Published: Dec. 13, 2023
Language: Английский
Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Language: Английский
Citations
0
Oncogenesis, Journal Year: 2025, Volume and Issue: 14(1)
Published: April 22, 2025
Fructose-1,6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis, is important for cancer progression. The post-translational regulation of FBP1 hypoxic environments still unclear. Here, we report that down-regulated, and low expression level predicts poor prognosis pancreatic cancer. A environment makes more prone to degradation, this effect can be reversed by inhibiting global O-GlcNAcylation signalling. O-linked N-acetylglucosamine transferase (OGT) interacts with induces its at serine 47 residue (FBP1-S47) modulate protein function cells. FBP1-S47 promotes degradation also influences the canonical HIF-1α target genes involved glucose metabolism, resulting an increase uptake lactate secretion In addition, facilitates K48-linked polyubiquitination lysine 51 (FBP1-K51), which GlcNAc moiety serve as prerequisite ubiquitin ligase. (K51) mediated promote progression, similarly FBP1-S47. Our data uncover mechanism whereby regulated O-GlcNAcylation-polyubiquitination axis, paving way cell metabolic reprogramming.
Language: Английский
Citations
0
Annals of the New York Academy of Sciences, Journal Year: 2025, Volume and Issue: unknown
Published: April 25, 2025
Abstract The intestines play important roles in responding immediately and dynamically to food intake, environmental stress, metabolic dysfunction, they are involved various human diseases aging. A key part of their function is governed by intestinal stem cells (ISCs); therefore, understanding ISCs vital. Dysregulation ISC activity, which influenced cell signaling pathways signals, can lead inflammatory responses, tissue damage, increased cancer susceptibility. Aging exacerbates these dynamics affects elasticity. Additionally, proliferation differentiation profoundly affect behavior gut health, highlighting the complex interplay between factors homeostasis. Drosophila models help us understand regulatory networks gut, providing valuable insights into disease mechanisms therapeutic strategies targeting diseases.
Language: Английский
Citations
0
Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(10)
Published: Oct. 19, 2024
Abstract The potential use of pro-senescence therapies, known as TIS (Therapy-Induced Senescence), for the treatment colorectal cancer (CRC) generated significant interest since they require lower doses compared to those required inducing apoptosis. However, senescent cell cycle-arrested cells are long-lived, and studies have revealed escape mechanisms contributing tumor recurrence. To deepen our understanding survival pathways used by cells, we delved into involvement hexosamine biosynthetic pathway (HBP). HBP provides UDP-GlcNAc, substrate O -GlcNAc transferase (OGT), which catalyzes -GlcNAcylation, a post-translational modification implicated in regulating numerous cellular functions aberrantly elevated CRC. In this study, demonstrated, p53-proficient colon lines HCT116 LS174T, that induced low-dose SN38 or etoposide was accompanied with decrease GFAT (the rate limiting enzyme HBP), OGT -GlcNAcase (OGA) expression correlated slight reduction -GlcNAcylation levels. Further decreasing level knocking-down redirected response subtoxic chemotherapy from senescence apoptosis, correlation an enhancement DNA damages. Pharmacological inhibition OSMI-4 LS174T patient-derived tumoroid model supported these findings. Taken together, results suggest combing inhibitors low conventional chemotherapeutic drugs could potentially reduce side effects while preserving efficacy. Furthermore, approach may increase specificity, CRC exhibit higher levels normal tissues.
Language: Английский
Citations
3
Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(44)
Published: Oct. 24, 2024
Aerobic glycolysis and immune evasion are two key hallmarks of cancer. However, how these features mechanistically linked to promote tumor growth is not well understood. Here, we show that the glycolytic enzyme enolase-1 (ENO1) dynamically modified with an
Language: Английский
Citations
3
Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(5), P. 107270 - 107270
Published: April 8, 2024
Higher demand for nutrients including glucose is characteristic of cancer. "Starving cancer" has been pursued to curb tumor progression. An ,intriguing regime inhibit transporter GLUT1 in cancer cells. In addition, during progression, cells may suffer from insufficient supply. Yet can somehow tolerate starvation. Uncovering the underlying mechanisms shall not only shed insight into progression but also benefit therapy. TFE3 a transcription factor known activate autophagic genes. Physiological activity regulated by phosphorylation-triggered translocation responsive nutrient status. We recently reported constitutively localizes cell nucleus and promotes proliferation kidney even under replete condition. Whether how responds starvation remain unclear. this study, we show resistance exposing physiologically relevant concentration. find triggers protein stabilization through increasing its O-GlcNAcylation. Furthermore, an unbiased functional genomic identify SLC36A1, lysosomal amino acid transporter, as target gene sensitive level. SLC36A1 overexpressed cancer, which mTOR proliferation. Importantly, level induced TFE3, enhances cellular Suppressing or significantly increases sensitivity inhibitor Collectively, uncover TFE3-SLC36A1 axis that tolerance
Language: Английский
Citations
2
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9896 - 9896
Published: Sept. 13, 2024
O-linked β-N-acetylglucosamine (O-GlcNAc, O-GlcNAcylation) is a post-translational modification of serine/threonine residues proteins. Alterations in O-GlcNAcylation have been implicated several types cancer, regulation tumor progression, inflammation, and thrombosis through its interaction with signaling pathways. We aim to explore the relationship between hemostasis, which could serve as potential prognostic tools or clinical predictions for cancer patients’ healthcare an approach combat cancer. found that characterized by high glucose demand consumption, chronic inflammatory state, state hypercoagulability, platelet hyperaggregability favors thrombosis; latter major cause death these patients. Furthermore, we review transcription factors pathways associated O-GlcNAcylation, thrombosis, such PI3K/Akt/c-Myc pathway, nuclear factor kappa B PI3K/AKT/mTOR pathway. also infectious agents inflammation inhibitors cell development. conclude it necessary both diagnosis treatment network multiple are integrated, search combination drugs regulate this network.
Language: Английский
Citations
2
Analytical and Bioanalytical Chemistry, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 18, 2024
Language: Английский
Citations
2
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 4022 - 4022
Published: April 4, 2024
A murine colorectal carcinoma (CRC) model was established. CT26 colon cells were injected into BALB/c mice’s spleen to study the primary tumor and mechanisms of cell spread cancer liver. The CRC verified by immunohistochemistry Pan Cytokeratin Vimentin expression. Immunophenotyping leukocytes isolated from CRC-bearing mice or healthy controls, such as CD19+ B cells, CD11+ myeloid CD3+ T carried out using fluorochrome-labeled lectins. binding six lectins white blood galectin-1 (Gal1), siglec-1 (Sig1), Sambucus nigra lectin (SNA), Aleuria aurantia (AAL), Phytolacca americana (PWM), galectin-3 (Gal3), assayed. Flow cytometric analysis splenocytes revealed increased SNA, AAL CD3 + CD11b cells; CD19 tumor-bearing mice. whole proteomic established liver versus tissues identified differentially expressed proteins, characteristic secondary tissues. KEGG Gene Ontology bioinformatic delineated protein interaction networks, biological pathways, cellular processes involved in CRC. Galectin-1 S100A4 upregulated proteins tissues, these previously reported contribute poor prognosis patients. Modelling development colonization injection may facilitate understanding carcinogenesis human novel therapeutic strategies.
Language: Английский
Citations
1
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: May 30, 2024
Abstract Idiopathic pulmonary fibrosis (IPF) is a lethal disease with substantial unmet medical needs. While aberrant epithelial remodelling key factor in IPF progression, the molecular mechanisms behind this process remain elusive. Using patient-derived 3D distal airway organoid model, we successfully recapitulate important features, including emergence of KRT5+/COL1A1+ basal cells and metabolic shift towards increased O-linked β-N-acetylglucosamine (O-GlcNAc) levels. Consistent this, single-cell analysis accessible chromatin reveals an accessibility these cells, particularly at JUNB motif-enriched promoter regions genes. O-GlcNAcylation shapes function promotes pro-fibrotic response to chronic injury, leading remodelling. Site-specific deletion on attenuates metaplastic differentiation thereby aiding restoration alveolar lineage. Together, data establish novel link between dysregulation, mediated by O-GlcNAc-JUNB axis, bronchiolization IPF, offering new therapeutic strategies treat fatal disease.
Language: Английский
Citations
1