Sphingolipid metabolism orchestrates establishment of the hair follicle stem cell compartment DOI Creative Commons
Franziska Peters,

Windie Höfs,

Hunki Lee

et al.

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(4)

Published: Jan. 29, 2025

Sphingolipids serve as building blocks of membranes to ensure subcellular compartmentalization and facilitate intercellular communication. How cell type–specific lipid compositions are achieved what is their functional significance in tissue morphogenesis maintenance has remained unclear. Here, we identify a stem cell–specific role for ceramide synthase 4 (CerS4) orchestrating fate decisions skin epidermis. Deletion CerS4 prevents the proper development adult hair follicle bulge (HFSC) compartment due altered differentiation trajectories. Mechanistically, HFSC defects arise from an imbalance key ceramides derivate sphingolipids, resulting hyperactivation noncanonical Wnt signaling. This impaired establishment leads disruption architecture barrier function, ultimately triggering T helper 2–dominated immune infiltration resembling human atopic dermatitis. work uncovers fundamental state–specific sphingolipid profile homeostasis maintaining intact barrier.

Language: Английский

Adipose-derived mesenchymal stem cells (MSCs) are a superior cell source for bone tissue engineering DOI Creative Commons
Yannian Gou, Yanran Huang,

Wenping Luo

et al.

Bioactive Materials, Journal Year: 2023, Volume and Issue: 34, P. 51 - 63

Published: Dec. 14, 2023

Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors, osteoinductive biofactors and biocompatible scaffold materials. Mesenchymal stem cells (MSCs) represent the most promising seed for engineering. As multipotent that can self-renew differentiate into multiple lineages including fat, MSCs be isolated from numerous tissues exhibit varied differentiation potential. To identify an optimal progenitor cell source engineering, we analyzed proliferative activity potential four commonly-used mouse MSC sources, immortalized embryonic fibroblasts (iMEF), marrow stromal (imBMSC), calvarial mesenchymal progenitors (iCAL), adipose-derived (iMAD). We found iMAD exhibited highest adipogenic capabilities upon BMP9 stimulation

Language: Английский

Citations

43
Fusobacterium nucleatum modulates the Wnt/β-catenin pathway in colorectal cancer development DOI

Tanushree Mondal,

Debasish Chattopadhyay, P. Mondal

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 299, P. 140196 - 140196

Published: Jan. 21, 2025

Language: Английский

Citations

2
Anticancer drugs: How to select small molecule combinations? DOI
Ruth Nussinov, Bengi Ruken Yavuz, Hyunbum Jang

et al.

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(6), P. 503 - 519

Published: May 22, 2024

Language: Английский

Citations

14
RNA 5-methylcytosine writer NSUN5 promotes hepatocellular carcinoma cell proliferation via a ZBED3-dependent mechanism DOI Creative Commons
Xinyu Gu, Penghui Li, Xiaohui Gao

et al.

Oncogene, Journal Year: 2024, Volume and Issue: 43(9), P. 624 - 635

Published: Jan. 5, 2024

Abstract Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer-related mortality worldwide. Nop2/Sun domain family member 5 (NSUN5), a conserved RNA 5-methylcytosine methyltransferase, conventionally recognized as oncogenic. However, its role in HCC development remains unknown. In this study, we observed remarkable upregulation NSUN5 expression both tumor tissues from patients with HCC, establishing correlation unfavorable clinical outcomes. knockdown and overexpression significantly inhibited promoted cell proliferation, respectively. Additionally, employing combination methylated immunoprecipitation sequencing (MeRIP-seq) RIP-seq techniques, identified zinc finger BED domain-containing protein 3 (ZBED3) novel downstream target NSUN5. found that ZBED3 counteracted tumor-suppressing effect simultaneously reversed inhibition Wnt/β-catenin signaling pathway. summary, elucidated oncogenic ZBED3/Wnt/β-catenin pathway target. This study provides therapeutic for further treatment.

Language: Английский

Citations

13
Targeting LRP6: A new strategy for cancer therapy DOI Creative Commons
Wei Xue, Bo Zhu, Kaili Zhao

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 204, P. 107200 - 107200

Published: May 6, 2024

Targeting specific molecular drivers of tumor growth is a key approach in cancer therapy. Among these targets, the low-density lipoprotein receptor-related protein 6 (LRP6), vital component Wnt signaling pathway, has emerged as an intriguing candidate. As cell-surface receptor and co-receptor, LRP6 frequently overexpressed various types, implicating its pivotal role driving progression. The pursuit target for treatment gained substantial traction, offering promising avenue therapeutic intervention. Here, this comprehensive review explores recent breakthroughs our understanding LRP6's functions underlying mechanisms, providing profound discussion involvement pathogenesis drug resistance. Importantly, we go beyond discussing by diverse potential approaches targeting enigmatic protein. These encompass wide spectrum, including pharmacological agents, natural compounds, non-coding RNAs, epigenetic factors, proteins, peptides that modulate expression or disrupt interactions. In addition, also discussed challenges associated with developing inhibitors their advantages over inhibitors, well drugs have entered phase II clinical trials. By shedding light on innovative strategies, aim to underscore significance valuable multifaceted treatment, igniting enthusiasm further research facilitating translation into applications.

Language: Английский

Citations

10
Innate versus adoptive competence: the controlled distribution of signalling receptors extends the concept of competence DOI Creative Commons

Jessica L. Bamsey,

Lucy Brunt, Steffen Scholpp

et al.

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

HighlightsA cell possesses competency if it expresses specific receptors and can thus react to complementary signalling ligands.Signalling ligands be disseminated via filopodia called cytonemes exovesicles such as exosomes.Cytonemes exosomes also transport receiving cells.Upon acquiring transferred receptors, cells the appropriate signal acquire adoptive competency.AbstractCellular communication through dissemination of molecules is vital for tissue organisation homeostasis. The mechanisms spreading include binding-protein-assisted transport, long membrane protrusions known cytonemes, exovesicles. Recent research indicates that not only but facilitate regulated distribution thereby enabling transduction in lacking endogenous receptors. This mechanism allows non-responsive temporarily ability respond ligands. review explores our understanding ligand receptor dispersal, offering fresh insights into fundamental concept cellular competence. Notably, these findings may have significant implications diseases their associated therapeutic targets, highlighting urgency importance this area.

Language: Английский

Citations

1
Triple-Negative Breast Cancer Progression and Drug Resistance in the Context of Epithelial–Mesenchymal Transition DOI Open Access
Ewa Błaszczak, Paulina Miziak, Adrian Odrzywolski

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 228 - 228

Published: Jan. 12, 2025

Triple-negative breast cancer (TNBC) is one of the most difficult subtypes to treat due its distinct clinical and molecular characteristics. Patients with TNBC face a high recurrence rate, an increased risk metastasis, lower overall survival compared other subtypes. Despite advancements in targeted therapies, traditional chemotherapy (primarily using platinum compounds taxanes) continues be standard treatment for TNBC, often limited long-term efficacy. tumors are heterogeneous, displaying diverse mutation profile considerable chromosomal instability, which complicates therapeutic interventions. The development chemoresistance frequently associated process epithelial–mesenchymal transition (EMT), during epithelial tumor cells acquire mesenchymal-like phenotype. This shift enhances metastatic potential, while simultaneously reducing effectiveness chemotherapeutics. It has also been suggested that EMT plays central role stem cells. Hence, there growing interest exploring small-molecule inhibitors target as future strategy overcoming resistance improving outcomes patients TNBC. review focuses on progression drug emphasis these processes. We present TNBC-specific EMT-related features, key protein markers, various signaling pathways involved. discuss important mechanisms factors related within context EMT, highlighting improve patients’ outcomes.

Language: Английский

Citations

1
A spotlight on the interplay between Wnt/β-catenin signaling and circular RNAs in hepatocellular carcinoma progression DOI Creative Commons
Alireza Mafi, Hamidreza Rismanchi, Mohaddese Malek Mohammadi

et al.

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

Published: July 21, 2023

Hepatocellular carcinoma (HCC) is one of the deadliest cancers due to multifocal development and distant metastasis resulting from late diagnosis. Consequently, new approaches HCC diagnosis treatment are required reduce mortality rates. A large body evidence suggests that non-coding RNAs (ncRNAs) important in cancer initiation progression. Cancer cells release many these ncRNAs into blood or urine, enabling their use as a diagnostic tool. Circular (CircRNAs) members regulate cell expansion, migration, metastasis, chemoresistance through different mechanisms such Wnt/β-catenin Signaling pathway. The pathway plays prominent roles several biological processes including organogenesis, stem regeneration, survival. Aberrant signaling both pathways mentioned above could affect progression cancers, HCC. Based on studies investigated current review, circRNAs have an effect formation by sponging miRNAs RNA-binding proteins (RBPs) regulating Therefore, circRNAs/miRNAs RBPs/Wnt/β-catenin be considered promising prognostic therapeutic targets

Language: Английский

Citations

21
Canonical and Non-Canonical Wnt Signaling Generates Molecular and Cellular Asymmetries to Establish Embryonic Axes DOI Creative Commons

De‐Li Shi

Journal of Developmental Biology, Journal Year: 2024, Volume and Issue: 12(3), P. 20 - 20

Published: Aug. 2, 2024

The formation of embryonic axes is a critical step during animal development, which contributes to establishing the basic body plan in each particular organism. Wnt signaling pathways play pivotal roles this fundamental process. Canonical that dependent on β-catenin regulates patterning dorsoventral, anteroposterior, and left–right axes. Non-canonical independent modulates cytoskeletal organization coordinate cell polarity changes asymmetric movements. It now well documented components these biochemically functionally interact mediate cell–cell communications instruct cellular polarization breaking symmetry. dysfunction disrupts axis specification proper tissue morphogenesis, mutations pathway genes are associated with birth defects humans. This review discusses regulatory by focusing vertebrate models. highlights current progress decoding conserved mechanisms underlying establishment asymmetry along three primary By providing an in-depth analysis canonical non-canonical regulating fates behaviors, work offers insights into intricate processes contribute setting up embryos.

Language: Английский

Citations

8
Compromised endothelial Wnt/β-catenin signaling mediates the blood-brain barrier disruption and leads to neuroinflammation in endotoxemia DOI Creative Commons
Xiaowen Huang,

Pengju Wei,

Cheng Fang

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Oct. 19, 2024

The blood-brain barrier (BBB) is a critical interface that maintains the central nervous system homeostasis by controlling exchange of substances between blood and brain. Disruption BBB plays vital role in development neuroinflammation neurological dysfunction sepsis, but mechanisms which becomes disrupted during sepsis are not well understood. Here, we induced endotoxemia, major type mice intraperitoneal injection lipopolysaccharide (LPS). LPS acutely increased permeability, activated microglia, heightened inflammatory responses brain endothelium parenchyma. Concurrently, or proinflammatory cytokines NF-κB pathway, inhibiting Wnt/β-catenin signaling endothelial cells vitro vivo. Cell culture study revealed p65 directly interacted with β-catenin to suppress signaling. Pharmacological pathway inhibition restored activity mitigated disruption septic mice. Furthermore, genetic pharmacological activation substantially alleviated LPS-induced leakage neuroinflammation, while conditional ablation Wnt7a/7b co-receptor Gpr124 exacerbated caused LPS. Mechanistically, rectified reduced expression levels tight junction protein ZO-1 transcytosis suppressor Mfsd2a both paracellular transcellular permeability BBB. Our findings demonstrate endotoxemia-associated systemic inflammation decreases through activating resulting acute neuroinflammation. Targeting may offer promising therapeutic strategy for preserving integrity treating sepsis.

Language: Английский

Citations

7