Tumor‐derived hypoxic small extracellular vesicles promote endothelial cell migration and tube formation via ALS2/Rab5/β‐catenin signaling DOI
Patricio Silva,

N. A. Hernandez,

Héctor Tapia

et al.

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(11)

Published: June 7, 2024

Abstract Tumor hypoxia has been associated with cancer progression, angiogenesis, and metastasis via modifications in the release cargo composition of extracellular vesicles secreted by tumor cells. Indeed, hypoxic are known to trigger a variety angiogenic responses different mechanisms. We recently showed that promotes endosomal signaling cells HIF‐1α‐dependent induction guanine exchange factor ALS2, which activates Rab5, leading downstream events involved cell migration invasion. Since Rab5‐dependent is required for endothelial we explored possibility small containing turn activate Rab5 recipient pro‐angiogenic properties. In doing so, found promoted ALS2 expression incorporation as within vesicles, subsequent transfer promoting migration, tube formation, activation. Consequently, ALS2‐containing increased early endosome size number cells, was followed sequestration components β‐catenin destruction complex compartments, stabilization nuclear localization β‐catenin. These converged target genes angiogenesis. Knockdown donor precluded its into preventing Rab5‐downstream responses, depended on activity ALS2. findings indicate vesicular hypoxia, Finally, these might explain how angiogenesis proceeds conditions.

Language: Английский

O-GlcNAcylation in cancer development and immunotherapy DOI

Xue-Fen He,

Xiaoli Hu,

Gao-Jing Wen

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 566, P. 216258 - 216258

Published: June 4, 2023

Language: Английский

Citations

43
FBXO31-mediated ubiquitination of OGT maintains O-GlcNAcylation homeostasis to restrain endometrial malignancy DOI Creative Commons
Na Zhang, Yang Meng,

Song Mao

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 2, 2025

Protein O-GlcNAcylation is a post-translational modification coupled to cellular metabolic plasticity. Aberrant has been observed in many cancers including endometrial cancer (EC), common malignancy women. However, clinical characterization of dysregulated homeostasis EC and interrogating its molecular mechanism remain incomplete. Here we report that level positively correlated with histologic grade Chinese cohort containing 219 tumors, validated The Cancer Genome Atlas dataset. Increasing patient-derived epithelial organoids promotes proliferation stem-like cell properties, whereas decreasing limits the growth organoids. CRISPR screen biochemical reveal tumor suppressor F-box only protein 31 (FBXO31) regulates by ubiquitinating O-GlcNAc transferase OGT. Downregulation impedes formation mouse models. Collectively, our study highlights as useful stratification marker therapeutic vulnerability for advanced, poorly differentiated cases. linked (EC). authors grade, FBXO31

Language: Английский

Citations

2
Identification of endothelial-related molecular subtypes for bladder cancer patients DOI Creative Commons
Dengxiong Li, Dechao Feng,

Xu Shi

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: March 21, 2023

Background Bladder cancer (BC) is a disease with significant heterogeneity and poor prognosis. The prognosis therapeutic response of BC patients are significantly influenced by endothelial cells in the tumor microenvironment. In order to understand from perspective cells, we orchestrated molecular subtypes identified key genes. Methods Single-cell bulk RNA sequencing data were extracted online databases. R its relative packages used analyze these data. Cluster analysis, prognostic value function immune checkpoints, environment prediction conducted. Results Five endothelial-related genes (CYTL1, FAM43A, HSPG2, RBP7, TCF4) divided TCGA, GSE13507, GSE32894 datasets into two clusters, respectively. cluster 2 substantially associated worse overall survival than those 1 according results GSE13507 datasets. functional clusters was enriched immune-related, metabolism-related pathways. Samples had statistically increase CD4+ T NK-cell infiltration. positively correlated stem score mutational burden score. analysis indicated that 50.6% (119/235) responded immunotherapy, while rate decreased 16.7% (26/155). Conclusion this study, categorized discovered distinctive prognosis-related at genetic level integrating single-cell data, primarily provide roadmap for precision medicine.

Language: Английский

Citations

25
Targeting O-GlcNAcylation in cancer therapeutic resistance: The sugar Saga continues DOI
Lulu Chen,

Mengxue Hu,

Luojun Chen

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 588, P. 216742 - 216742

Published: Feb. 23, 2024

Language: Английский

Citations

11
Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis DOI Creative Commons

Lingfeng Bi,

Xin Wang, Jiayi Li

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: Feb. 21, 2025

Abstract The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, noncoding RNA changes, often precede genetic mutations are critical in progression. In this study, we explore how biopsy, combined markers, can provide cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges targeting regulators, which could disrupt cellular balance if overexploited, need maintaining key gene expressions therapeutic applications. This review highlights promise using early‐stage diagnosis, a focus on optimizing treatment strategies precision medicine.

Language: Английский

Citations

1
Bladder Cancer‐Derived Small Extracellular Vesicles Promote Tumor Angiogenesis by Inducing HBP‐Related Metabolic Reprogramming and SerRS O‐GlcNAcylation in Endothelial Cells DOI Creative Commons
Xinyuan Li,

Xiang Peng,

Chunlin Zhang

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 9(30)

Published: Aug. 31, 2022

Abstract A malformed tumour vascular network provokes the nutrient‐deprived microenvironment (TME), which conversely activates endothelial cell (EC) functions and stimulates neovascularization. Emerging evidence suggests that flexible metabolic adaptability of cells helps to establish a symbiosis among various subpopulations in fluctuating TME. In this study, authors propose novel link between bladder cancer (BCa) ECs nutrient‐scarce TME, BCa‐secreted glutamine‐fructose‐6‐phosphate aminotransferase 1 (GFAT1) via small extracellular vesicles (sEVs) reprograms glucose metabolism by increasing hexosamine biosynthesis pathway flux thus enhances O‐GlcNAcylation. Moreover, seryl‐tRNA synthetase (SerRS) O‐GlcNAcylation at serine 101 promotes its degradation ubiquitination impeded importin α 5‐mediated nuclear translocation. Intranuclear SerRS attenuates growth factor transcription competitively binding GC‐rich region proximal promotor. Additionally, GFAT1 knockout blocks angiogenesis both vitro vivo. However, administration GFAT1‐overexpressing BCa cells‐derived sEVs increase angiogenetic activity GFAT1‐knockout mice. summary, study inhibiting sEV‐mediated secretion from targeting may serve as strategies for antiangiogenetic therapy.

Language: Английский

Citations

32
Small extracellular vesicles delivering lncRNA WAC-AS1 aggravate renal allograft ischemia‒reperfusion injury by inducing ferroptosis propagation DOI
Xinyuan Li,

Xiang Peng,

Xiang Zhou

et al.

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(9), P. 2167 - 2186

Published: Aug. 2, 2023

Language: Английский

Citations

22
Canagliflozin reduces chemoresistance in hepatocellular carcinoma through PKM2-c-Myc complex-mediated glutamine starvation DOI
Yuan Zeng, Haoran Jiang,

Xiangting Zhang

et al.

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 208, P. 571 - 586

Published: Sept. 9, 2023

Language: Английский

Citations

19
The interplay between the tumor microenvironment and tumor-derived small extracellular vesicles in cancer development and therapeutic response DOI Creative Commons

Xuanyu Guo,

Jiajun Song, Miao Liu

et al.

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: May 20, 2024

The tumor microenvironment (TME) plays an essential role in cell survival by profoundly influencing their proliferation, metastasis, immune evasion, and resistance to treatment. Extracellular vesicles (EVs) are small particles released all types often reflect the state of parental cells modulate other cells' functions through various cargo they transport. Tumor-derived EVs (TDSEVs) can transport specific proteins, nucleic acids lipids tailored propagate signals establish a favorable TME. Thus, TME's biological characteristics affect TDSEV heterogeneity, this interplay amplify growth, dissemination, therapy. This review discusses between TME TDSEVs based on summarizes strategies for targeting cancer cells. Additionally, it reviews current issues challenges field offer fresh insights into comprehending development mechanisms exploring innovative clinical applications.

Language: Английский

Citations

7
Lactylation in cancer: Mechanisms in tumour biology and therapeutic potentials DOI Creative Commons
Yipeng He,

Tianbao Song,

Jinzhuo Ning

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(11)

Published: Oct. 25, 2024

Lactylation, a recently identified form of protein post-translational modification (PTM), has emerged as key player in cancer biology. The Warburg effect, hallmark tumour metabolism, underscores the significance lactylation progression. By regulating gene transcription and function, facilitates metabolic reprogramming, enabling tumours to adapt nutrient limitations sustain rapid growth. Over past decade, extensive research revealed intricate regulatory network underlying tumours. Large-scale sequencing machine learning have confirmed widespread occurrence sites across proteome. Targeting enzymes or pathways demonstrated promising anti-tumour effects, highlighting therapeutic potential this modification. This review comprehensively explores mechanisms cells microenvironment. We expound on application advanced omics technologies for target identification data modelling within field. Additionally, we summarise existing anti-lactylation drugs discuss their clinical implications. providing comprehensive overview recent advancements, aims stimulate innovative accelerate translation lactylation-based therapies into practice. KEY POINTS: Lactylation significantly influences metabolism regulation, contributing Advanced reveal shows promise enhancing drug efficacy overcoming chemotherapy resistance. outlines implications future directions oncology.

Language: Английский

Citations

6