Notch Signaling in Breast Tumor Microenvironment as Mediator of Drug Resistance DOI Open Access
Adele Chimento,

Maria D’Amico,

Vincenzo Pezzi

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(11), P. 6296 - 6296

Published: June 4, 2022

Notch signaling dysregulation encourages breast cancer progression through different mechanisms such as stem cell maintenance, proliferation and migration/invasion. Furthermore, is a crucial driver regulating juxtracrine paracrine communications between tumor stroma. The complex interplay the abnormal pathway orchestrating activation of other signals cellular heterogeneity contribute towards remodeling microenvironment. These changes, together with evolution treatment pressure, drive drug resistance. Preclinical studies have shown that targeting can prevent or reverse resistance, reducing eliminating cells. In present review, we will summarize current scientific evidence highlights involvement within microenvironment, angiogenesis, extracellular matrix remodeling, tumor/stroma/immune system its in therapy

Language: Английский

Mechanistic Pathogenesis of Endothelial Dysfunction in Diabetic Nephropathy and Retinopathy DOI Creative Commons
Jing Yang, Zhangsuo Liu

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: May 25, 2022

Diabetic nephropathy (DN) and diabetic retinopathy (DR) are microvascular complications of diabetes. Microvascular endothelial cells thought to be the major targets hyperglycemic injury. In microvasculature, intracellular hyperglycemia causes damages vascular endothelium, via multiple pathophysiological process consist inflammation, cell crosstalk with podocytes/pericytes exosomes. addition, DN DR diseases development involved in several critical regulators including adhesion molecules (CAMs), growth factor (VEGF) family Notch signal. The present review attempts gain a deeper understanding pathogenesis complexities underlying dysfunction diabetes retinopathy, contributing new mechanistic therapeutic strategies against diabetes-induced dysfunction.

Language: Английский

Citations

146
A concise review of VEGF, PDGF, FGF, Notch, angiopoietin, and HGF signalling in tumor angiogenesis with a focus on alternative approaches and future directions DOI
Selvaraj Vimalraj

International Journal of Biological Macromolecules, Journal Year: 2022, Volume and Issue: 221, P. 1428 - 1438

Published: Sept. 17, 2022

Language: Английский

Citations

98
MultiNicheNet: a flexible framework for differential cell-cell communication analysis from multi-sample multi-condition single-cell transcriptomics data DOI Creative Commons
Robin Browaeys, Jeroen Gilis, Chananchida Sang-aram

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 14, 2023

Abstract Dysregulated cell-cell communication is a hallmark of many disease phenotypes. Due to recent advances in single-cell transcriptomics and computational approaches, it now possible study intercellular on genome- tissue-wide scale. However, most current inference tools have limitations when analyzing data from multiple samples conditions. Their main limitation that they do not address inter-sample heterogeneity adequately, which could lead false inference. This issue crucial for human cohort scRNA-seq datasets, complicating the comparison between healthy diseased subjects. Therefore, we developed MultiNicheNet ( https://github.com/saeyslab/multinichenetr ), novel framework better analyze multi-sample multi-condition data. The goals are inferring differentially expressed active ligand-receptor pairs conditions interest predicting putative downstream target genes these pairs. To achieve this goal, applies principles state-of-the-art differential expression algorithms As result, users can while adequately addressing heterogeneity, handling complex multifactorial experimental designs, correcting batch effects covariates. Moreover, uses NicheNet-v2, our new substantially improved version NicheNet’s network ligand-target prior knowledge model. We applied patient several diseases (breast cancer, squamous cell carcinoma, multisystem inflammatory syndrome children, lung fibrosis). For diseases, uncovered known aberrant signaling processes. also demonstrated MultiNicheNet’s potential perform non-trivial analysis tasks, such as studying between- within-group differences dynamics response therapy. final example, used MulitNicheNet elucidate dysregulated idiopathic pulmonary fibrosis integrated atlas Given anticipated increase datasets due technological advancements extensive atlas-building integration efforts, expect will be valuable tool uncover states.

Language: Английский

Citations

71
HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies DOI Creative Commons
Yan Zhao, Cheng Xing,

Yating Deng

et al.

Genes & Diseases, Journal Year: 2023, Volume and Issue: 11(1), P. 234 - 251

Published: March 30, 2023

Language: Английский

Citations

60
A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer’s disease DOI Creative Commons
Stergios Tsartsalis, Hannah Sleven, Nurun Fancy

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 12, 2024

Brain perfusion and blood-brain barrier (BBB) integrity are reduced early in Alzheimer's disease (AD). We performed single nucleus RNA sequencing of vascular cells isolated from AD non-diseased control brains to characterise pathological transcriptional signatures responsible for this. show that endothelial (EC) enriched expression genes associated with susceptibility AD. Increased β-amyloid is BBB impairment a dysfunctional angiogenic response related failure increased pro-angiogenic HIF1A VEGFA signalling EC. This inflammatory activation, EC senescence apoptosis. Our genomic dissection cell risk gene enrichment provides evidence role pathology suggests reducing activation restoring effective angiogenesis could reduce dysfunction contributing the genesis or progression

Language: Английский

Citations

29
The role of laminins in cancer pathobiology: a comprehensive review DOI Creative Commons

Elena Nonnast,

E. Mira, Santos Mañes

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 17, 2025

Laminins (LMs) are a family of heterotrimeric glycoproteins that form the structural foundation basement membranes (BM). By acting as molecular bridges between cells and extracellular matrix (ECM) through integrins other surface receptors, they regulate key cellular signals influence cell behavior tissue architecture. Despite their physiological importance, our understanding role LMs in cancer pathobiology remains fragmented. In this article, we review diverse functions promoting proliferation, adhesion, migration-critical steps metastasis. Beyond direct effects on tumor cells, stromal interactions modulate microenvironment dynamics, affecting processes such angiogenesis, immune infiltration, cancer-associated fibroblast activation, evasion. Understanding complex roles biology, well differential expression patterns malignancies, could provide new diagnostic tools for predicting disease outcomes pave way innovative therapeutic strategies, targeting LM-receptor or modulating ECM dynamics to impede growth

Language: Английский

Citations

2
Adipose mesenchymal stem cells combined with platelet-rich plasma accelerate diabetic wound healing by modulating the Notch pathway DOI Creative Commons

Nesrine Ebrahim,

Arigue A. Dessouky, Ola Mostafa

et al.

Stem Cell Research & Therapy, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 13, 2021

Abstract Background Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due to its content growth factors. However, application limited the rapid degradation The present study aimed evaluate efficacy combined adipose-derived mesenchymal stem cells (ADSCs) PRP therapy in promoting relation Notch signaling pathway. Methods Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic), diabetic, PRP-treated, ADSC-treated, PRP+ADSCs-treated groups]. effect individual was evaluated assessing closure rate, epidermal thickness, dermal collagen, angiogenesis. Moreover, gene protein expression key elements pathway (Notch1, Delta-like canonical ligand 4 (DLL4), Hairy Enhancer Split-1 (Hes1), Hey1, Jagged-1), angiogenic marker (vascular endothelial factor stromal cell-derived 1) (EPSCs) related (ß1 Integrin) assessed. Results Our data showed better PRP+ADSCs compared their use after 7 14 days as caused reepithelialization granulation tissue formation with marked increase area percentage significantly downregulated, EPSC proliferation recruitment enhanced other treated groups. Conclusions These demonstrated that ADSCs accelerated wounds induced experimentally via modulating pathway, angiogenesis proliferation.

Language: Английский

Citations

68
Targeting the DLL/Notch Signaling Pathway in Cancer: Challenges and Advances in Clinical Development DOI Creative Commons
Weon‐Kyoo You, Thomas Schuetz, Sang Hoon Lee

et al.

Molecular Cancer Therapeutics, Journal Year: 2022, Volume and Issue: 22(1), P. 3 - 11

Published: Oct. 12, 2022

Abstract The DLL/Notch signaling pathway plays an important role in cancer as a key driver maintaining stemness and inducing tumor angiogenesis. Many different types of inhibitors have been developed explored clinical trials for treatment, including small-molecule compounds to inhibit gamma-secretase antibodies targeting Notch ligands or receptors. Despite promising efficacy these preclinical studies, the overall outcomes insufficient advance next stage development primarily due safety concerns modest efficacy. To overcome narrow therapeutic window inhibitors, diverse strategies improving balance between are currently being explored. Here, we review perspective potential anticancer agents based on recent results from multiple studies. An antibody specifically receptors may offer better approach reduce about toxicity derived broad-spectrum blockers. In addition, combination therapy with angiogenesis inhibitor VEGF could be option increasing Taken together, suggest bispecific blocking VEGF/VEGFR pathways effective treatment.

Language: Английский

Citations

40
Notch Signaling in Acute Inflammation and Sepsis DOI Open Access
Nadia Gallenstein, Lucas Tichy, Markus Weigand

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3458 - 3458

Published: Feb. 9, 2023

Notch signaling, a highly conserved pathway in mammals, is crucial for differentiation and homeostasis of immune cells. Besides, this also directly involved the transmission signals. signaling per se does not have clear pro- or anti-inflammatory effect, but rather its impact dependent on cell type cellular environment, modulating several inflammatory conditions including sepsis, therefore significantly impacts course disease. In review, we will discuss contribution clinical picture systemic diseases, especially sepsis. Specifically, review role during development to modulation organ-specific responses. Finally, evaluate what extent manipulation could be future therapeutic strategy.

Language: Английский

Citations

35
Notch signaling, hypoxia, and cancer DOI Creative Commons
Mingzhou Guo,

Yang Niu,

Min Xie

et al.

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

Published: Jan. 31, 2023

Notch signaling is involved in cell fate determination and deregulated human solid tumors. Hypoxia an important feature many tumors, which activates hypoxia-induced factors (HIFs) their downstream targets to promote tumorigenesis cancer development. Recently, HIFs have been shown trigger the pathway a variety of organisms tissues. In this review, we focus on pro- anti-tumorigenic functions discuss crosstalk between cellular hypoxic response pathogenesis, including epithelia-mesenchymal transition, angiogenesis, maintenance stem cells. The pharmacological strategies targeting hypoxia are also discussed review.

Language: Английский

Citations

26