The origin and evolution of Wnt signalling

Nature Reviews Genetics, Год журнала: 2024, Номер 25(7), С. 500 - 512

Опубликована: Фев. 19, 2024

Язык: Английский

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Generation of multilineage liver organoids with luminal vasculature and bile ducts from human pluripotent stem cells via modulation of Notch signaling

Stem Cell Research & Therapy, Год журнала: 2023, Номер 14(1)

Опубликована: Фев. 3, 2023

Abstract Background The generation of liver organoids recapitulating parenchymal and non-parenchymal cell interplay is essential for the precise in vitro modeling diseases. Although different types multilineage (mLOs) have been generated from human pluripotent stem cells (hPSCs), assembly concurrent differentiation multiple individual mLOs remain a major challenge. Particularly, most studies focused on vascularization host tissue after transplantation vivo. However, relatively little information available formation luminal vasculature themselves. Methods with blood vessels bile ducts were by assembling hepatic endoderm, stellate cell-like (HscLCs), endothelial derived entirely hPSCs using 96-well ultra-low attachment plates. We analyzed effect HscLC incorporation Notch signaling modulation both immunofluorescence staining, qRT-PCR, ELISA, live-perfusion imaging. potential use fibrosis was evaluated histological gene expression analyses treatment pro-fibrotic cytokines. Results found that hPSC-derived HscLCs are crucial generating functional microvasculature mLOs. subsequent substantially reduced apoptotic death promoted survival growth microvessels. In particular, during specific time window organoid critical vasculature. Live-cell imaging, series confocal scans, electron microscopy demonstrated well distributed inside had perfusable lumens vitro. addition, exposure to cytokines induced early fibrosis-associated events, including upregulation genes associated fibrotic induction activation (i.e., collagen I, α -SMA, ICAM) together destruction architecture shrinkage. Conclusion Our results demonstrate can reproduce interactions suggest their application advance diseases

Язык: Английский

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Innate versus adoptive competence: the controlled distribution of signalling receptors extends the concept of competence

Trends in Cell Biology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 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.

Язык: Английский

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Therapeutic Potential of Naturally Occurring Small Molecules to Target the Wnt/β-Catenin Signaling Pathway in Colorectal Cancer

Cancers, Год журнала: 2022, Номер 14(2), С. 403 - 403

Опубликована: Янв. 14, 2022

Colorectal cancer (CRC) ranks second in the number of deaths worldwide, mainly due to late diagnoses, which restrict treatment potentially curable stages and decrease patient survival. The CRC involves surgery remove tumor tissue, addition radiotherapy systemic chemotherapy sessions. However, almost half patients are resistant these treatments, especially metastatic cases, where 5-year survival rate is only 12%. This factor may be related intratumoral heterogeneity, microenvironment (TME), presence stem cells (CSCs), impossible resolve with standard approaches currently available clinical practice. CSCs APC-deficient, search for alternative therapeutic agents such as small molecules from natural sources a promising strategy, substances have several antitumor properties. Many those interfere regulation signaling pathways at central core development, Wnt/β-catenin, plays crucial role cell proliferation stemness tumor. review will discuss use naturally occurring inhibiting Wnt/β-catenin pathway experimental models over past decade, highlighting molecular targets mechanisms through perform their activities.

Язык: Английский

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The Roles of Secreted Wnt Ligands in Cancer

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5349 - 5349

Опубликована: Март 10, 2023

Wnt ligands are secreted signaling proteins that display a wide range of biological effects. They play key roles in stimulating pathways to facilitate processes such as tissue homeostasis and regeneration. Dysregulation is hallmark many cancers genetic alterations various components, which result ligand-independent or ligand-dependent hyperactivation the pathway have been identified. Recently, research focusing on impact interaction between tumor cells their micro-environment. This Wnt-mediated crosstalk can act either promoting suppressing fashion. In this review, we comprehensively outline function different entities phenotypes, including cancer stemness, drug resistance, metastasis, immune evasion. Lastly, elaborate approaches target therapy.

Язык: Английский

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Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Апрель 2, 2025

The Wnt signaling pathway plays a crucial role in development and tissue homeostasis, regulating key cellular processes such as proliferation, differentiation, apoptosis. However, its abnormal activation is strongly associated with tumorigenesis, metastasis, resistance to therapy, making it vital target for cancer treatment. This review provides comprehensive insight into the of cancer, examining normal physiological functions, dysregulation malignancies, therapeutic potential. We emphasize importance predicting sensitivity identify biomarkers across various types. Additionally, we address challenges future prospects Wnt-targeted therapies, including biomarker discovery, advancements emerging technologies, their application clinical practice.

Язык: Английский

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Frizzled2 receives WntA signaling during butterfly wing pattern formation

Development, Год журнала: 2023, Номер 150(18)

Опубликована: Авг. 21, 2023

ABSTRACT Butterfly color patterns provide visible and biodiverse phenotypic readouts of the patterning processes. Although secreted ligand WntA has been shown to instruct pattern formation in butterflies, its mode reception remains elusive. genomes encode four homologs Frizzled-family Wnt receptors. Here, we show that CRISPR mosaic knockouts frizzled2 (fz2) phenocopy effects loss function multiple nymphalids. Whereas clones result intermediate reduced size, fz2 are cell-autonomous, consistent with a morphogen function. Shifts expression crispant pupae they under positive negative feedback, respectively. Fz1 is required for Wnt-independent planar cell polarity wing epithelium. Fz3 Fz4 phenotypes competitive-antagonist functions vein (Fz3 Fz4), margin specification (Fz3), Discalis Marginal Band Systems (Fz4). Overall, these data WntA/Frizzled2 morphogen-receptor pair forms signaling axis instructs butterfly shed light on functional diversity insect Frizzled

Язык: Английский

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Wnt Pathway in Pancreatic Development and Pathophysiology

Cells, Год журнала: 2023, Номер 12(4), С. 565 - 565

Опубликована: Фев. 9, 2023

The pancreas is an abdominal gland that serves 2 vital purposes: assist food processing by secreting digestive enzymes and regulate blood glucose levels releasing endocrine hormones. During embryonic development, this originates from epithelial buds located on opposite sites of the foregut endoderm. Pancreatic cell specification maturation are coordinated a complex interplay extrinsic intrinsic signaling events. In recent years, canonical Wnt/β-catenin pathway has emerged as important player organogenesis, regulating pancreatic epithelium specification, compartmentalization expansion. Importantly, it been suggested to proliferation, survival function adult cells, including insulin-secreting β-cells. This review summarizes work role in biology early development adulthood, emphasizing its relevance for new therapies diseases.

Язык: Английский

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New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis

In Vitro Cellular & Developmental Biology - Animal, Год журнала: 2024, Номер 60(5), С. 449 - 465

Опубликована: Фев. 21, 2024

Abstract Wnt signaling plays a crucial role in embryonic development and homeostasis maintenance. Delicate sensitive fine-tuning of based on the proper timings positions is required to balance cell proliferation differentiation maintain individual health. Therefore, broken by tissue hypoplasia or tumor formation once signal dysregulation disturbs proliferation. The well-known regulatory mechanism molecular reaction associated with cytoplasmic accumulation effector β-catenin. In addition β-catenin, most proteins are also regulated ubiquitin-dependent modification, both qualitatively quantitatively. This review will explain regulation whole four phases, as well different ubiquitin ligases function deubiquitinating enzymes each phase. Along recent results, which RNF43 negatively regulates surface expression receptors, has recently been understood, be detailed. Many mutations have identified pancreatic gastrointestinal cancers examined for their functional alteration signaling. Several facilitate activate signal, reversing suppressor into an oncogene. may simultaneously play roles classical multistep tumorigenesis, wild-type mutant suppress p53 pathway. We hope that knowledge obtained from further research applied cancer treatment future despite fully unclear RNF43.

Язык: Английский

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Pharmacological modulation of Sonic Hedgehog signaling pathways in Angiogenesis: A mechanistic perspective

Developmental Biology, Год журнала: 2023, Номер 504, С. 58 - 74

Опубликована: Сен. 20, 2023

Язык: Английский

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