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

An Overview of Angiogenesis in Bladder Cancer DOI Creative Commons
Ghada Elayat,

Ivan Punev,

Abdel Selim

et al.

Current Oncology Reports, Journal Year: 2023, Volume and Issue: 25(7), P. 709 - 728

Published: April 13, 2023

Angiogenesis plays a key role in bladder cancer (BC) pathogenesis. In the last two decades, an increasing number of publications depicting multitude novel angiogenic molecules and pathways have emerged. The growing complexity necessitates evaluation breadth current knowledge to highlight findings guide future research.

Language: Английский

Citations

16
Environmental cadmium exposure facilitates mammary tumorigenesis via reprogramming gut microbiota-mediated glutamine metabolism in MMTV-Erbb2 mice DOI
Yue Yang,

Huadong Zhang,

Ping Deng

et al.

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 897, P. 165348 - 165348

Published: July 8, 2023

Language: Английский

Citations

14
O-GlcNAcylation in tumorigenesis and its implications for cancer therapy DOI Creative Commons

Dize Zhang,

Yihang Qi, Hiroyuki Inuzuka

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(9), P. 107709 - 107709

Published: Aug. 22, 2024

O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a dynamic and reversible posttranslational modification that targets serine threonine residues in variety of proteins. Uridine diphospho-N-acetylglucosamine, which synthesized from glucose via the hexosamine biosynthesis pathway, major donor this modification. O-GlcNAc transferase sole enzyme transfers GlcNAc onto protein substrates, while O-GlcNAcase responsible for removing O-GlcNAcylation plays an important role tumorigenesis progression through specific substrates. In review, we discuss tumor-related biological functions summarize recent progress development pharmaceutical options to manipulate proteins as potential anticancer therapies.

Language: Английский

Citations

5
Magnetic 3D macroporous MOF oriented urinary exosome metabolomics for early diagnosis of bladder cancer DOI Creative Commons

Yiqing Cao,

Jianan Feng,

Qiao Zhang

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 2, 2024

Bladder cancer (BCa) exhibits the escalating incidence and mortality due to untimely inaccurate early diagnosis. Urinary exosome metabolites, carrying critical tumor cell information directly related bladder, emerge as promising non-invasive diagnostic biomarkers of BCa. Herein, magnetic 3D ordered macroporous zeolitic imidazolate framework-8 (magMZIF-8) is synthesized used for efficient urinary isolation. Notably, beyond retaining single crystals micropores conventional ZIF-8, MZIF-8 further enhanced with highly oriented macropores (150 nm) large specific surface area (973 m

Language: Английский

Citations

4
Diagnostic value of dual-layer spectral detector CT parameters for differentiating high- from low-grade bladder cancer DOI Creative Commons
Li Chen, Lili Xu, Xiaoxiao Zhang

et al.

Insights into Imaging, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Abstract Objectives This study aimed to investigate the diagnostic value of spectral parameters dual-layer detector computed tomography (DLCT) in distinguishing between low- and high-grade bladder cancer (BCa). Methods single-center retrospective included pathologically confirmed BCa patients who underwent preoperative contrast-enhanced DLCT. Patients were divided into groups based on pathology. We measured calculated following CT parameters: iodine density (ID), normalized ID (NID), arterial enhancement fraction (AEF), extracellular volume (ECV) fraction, virtual non-contrast (VNC), slope attenuation curve, Z effective (Z eff ). Univariate multivariable logistic regression analyses used determine best predictive factors differentiating BCa. receiver operating characteristic curve analysis assess performance decision net benefit. Results The 64 (mean age, ± 11.0 years; 46 men), whom 42 had 22 low-grade revealed that differences NID corticomedullary phase, AEF, ECV, VNC, images statistically significant ( p = 0.001–0.048). Multivariable found AEF was predictor tumors 0.006). With higher BCa, results as follows: area under (AUC), 0.924 (95% confidence interval, 0.861–0.988); sensitivity, 95.5%; specificity, 81.0%; accuracy, 85.9%. cutoff valve for predicting 67.7%. Conclusion Using DLCT could help distinguish from Critical relevance statement research demonstrates a parameter derived (DLCT), effectively distinguishes high- cancer, thereby aiding selection appropriate clinical treatment strategies. Key Points investigated assessment (BCa) histological grade. Our can clinicians formulate initial strategies improve prognostications. Graphical

Language: Английский

Citations

0
Exosomes containing miR-152-3p targeting FGFR3 mediate SLC7A7-induced angiogenesis in bladder cancer DOI Creative Commons
Chun Cao, Yu Wang, Xiaolin Deng

et al.

npj Precision Oncology, Journal Year: 2025, Volume and Issue: 9(1)

Published: March 12, 2025

Abstract Bladder cancer (BCa) is a prevalent malignancy with poor prognosis. SLC7A7 has been linked to BCa progression and angiogenesis, but its specific role remains unclear. We established SLC7A7-knockdown cell line investigate effects on angiogenesis. In vivo experiments assessed tumor vascularization, while in vitro studies explored exosome involvement. MiRNA sequencing identified miR-152-3p as key regulator. Further investigation using dual-luciferase reporter assays, qRT-PCR, Western blot revealed that inhibits the expression of FGFR3 by binding 3’ UTR. Meanwhile, functional including angiogenesis Transwell wound healing were performed evaluate confirmed significant progression, specifically promoting through involvement exosomes regulatory axis miR-152-3p/ FGFR3. Targeting might be promising strategy reverse control for an improved

Language: Английский

Citations

0
Starvation-induced HBP metabolic reprogramming and STAM2 O-GlcNAcylation facilitate bladder cancer metastasis DOI Creative Commons

Zhenwei Feng,

Yuhua Mei,

Haonan Chen

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 12, 2025

Metabolic reprogramming and epigenetic alternations are implicated in tumor progression metastasis, but the metabolic mechanisms underlying lymphatic distant metastasis of bladder cancer (BCa) remain poorly understood. In this study, we provide first evidence that glutamine-fructose-6-phosphate aminotransferase 1 (GFAT1), crucial rate-limiting switch hexosamine biosynthesis pathway (HBP), is considerably upregulated nutrient-scarce microenvironment causes a high O-GlcNAcylation signal transducing adaptor molecule 2 (STAM2), further facilitating BCa. Inhibition GFAT1 impairs STAM2-induced metastasis. Mechanistically, STAM2 at serine 375 augments protein stability by inhibiting proteasome degradation ubiquitination. addition, facilitates Janus kinase (JAK2) transducer activator transcription (STAT3) phosphorylation, thus activating epithelial‒mesenchymal transition. summary, these results reveal novel link mediating indicate targeting may serve as promising treatment strategy for BCa progression.

Language: Английский

Citations

0
The multifaceted roles of small extracellular vesicles in metabolic reprogramming in the tumor microenvironments DOI
Zhixian Chen, Judy Wai Ping Yam, Xiaowen Mao

et al.

PROTEOMICS, Journal Year: 2024, Volume and Issue: 24(11)

Published: Jan. 3, 2024

Abstract The link between metabolism and tumor progression has been extensively researched for a long time. With the increasing number of studies uncovering multiple functions metabolic reprogramming in microenvironments, regulatory network seems to become even more intricate at same Small extracellular vesicles (sEV), as crucial mediators facilitating intercellular communications, exhibit significant involvement regulating within complicated microenvironments. sEV derived from cells those released by other cell populations such tumor‐associated macrophages (TAMs) cancer‐associated fibroblasts (CAFs) can mutually influence each other, giving rise diverse complex feedback loops. This review includes conducted recent years summarize altering various types Additionally, it aims highlight potential therapeutic targets based on commonly observed mechanisms identified different studies.

Language: Английский

Citations

3
Crosstalk between bladder cancer and the tumor microenvironment: Molecular mechanisms and targeted therapy DOI

Xiaole Lu,

Liang Cheng, Chenwei Yang

et al.

The Innovation Medicine, Journal Year: 2024, Volume and Issue: unknown, P. 100094 - 100094

Published: Jan. 1, 2024

<p>Bladder cancer (BCa) is the most common and lethal urological malignancy. Lymphatic metastasis main type of a poor prognostic factor for bladder patients. Although several treatments are approved BCa patients, some patients still resistant to current therapy. The tumor microenvironment (TME), which consists diverse cellular components, crucial mediator progression treatment resistance. However, literature on interactions between TME lacks coherence systematic analysis, while impact intratumoral heterogeneity (ITH) tumorigenesis has not been fully summarized. Iterative insights into factors intrinsic extrinsic cells that regulate response critically needed. Here, we provide an overview knowledge multilevel crosstalk TME, including protein-coding genes epigenetic in cells, tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), neutrophils (TANs), endothelial (ECs), lymphatic (LECs) other play roles tumorigenesis, progression, development drug We also summarize advanced therapeutic approaches targeting discuss challenges future perspectives associated with therapies.</p>

Language: Английский

Citations

3
Glycometabolic Regulation of Angiogenesis: Mechanisms and Therapeutic Strategies DOI Open Access
Zhifeng Yao, Junting Li,

Jiaming Yu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2386 - 2386

Published: March 7, 2025

Angiogenesis, the process by which new blood vessels emerge from pre-existing vasculature, forms fundamental biological basis for therapeutic angiogenesis. In recent years, this field has garnered significant attention, particularly in context of understanding mechanisms angiogenesis through lens glycometabolism. The potential clinical applications research have been widely acknowledged within medical community. article, role and principal molecular that govern it are first delineated. influence glycometabolism on is then explored, with a focus glycolysis. Finally, based regulation presented, offering novel perspectives ongoing applications.

Language: Английский

Citations

0