Wnt/β-catenin signaling in development and cancer

β-catenin-independent regulation by TCF7L2 underlies isoform redundancy during embryonic thalamic development

The paper investigates TCF7L2 isoform redundancy in thalamic development, finding β-catenin-independent regulation and a developmental switch in activity.

Wnt/β-catenin signaling promotes zebrafish osteoblast dedifferentiation by wnt10a-mediated inhibition of NF-κB

The paper shows that Wnt/β-catenin signaling via wnt10a inhibits NF-κB to induce osteoblast dedifferentiation in zebrafish, which is also observed in cardiomyocytes during heart regeneration.

Comparison between the activities of canonical Wnt ligands in human pluripotent stem cell differentiation

The paper compares the activities of canonical Wnt ligands in human pluripotent stem cell differentiation and finds differences in their ability to induce mesodermal and ectodermal markers.

Hepatocellular carcinoma-associated AXIN1 mutations drive low levels of Wnt/β-catenin pathway activity that allow for niche-independent growth and YAP/TAZ signaling

This study shows that AXIN1 mutations in HCC lead to reduced Wnt/β-catenin activity and increased YAP/TAZ signaling, enabling niche-independent growth.

TOE1 influences canonical Wnt signalling in myeloid leukaemia cells through LEF-1 modulation and regulates the proliferation of haematopoietic cells through PAK2.

This study identifies TOE1 as a novel β-catenin interactor in myeloid cells that modulates Wnt signaling via LEF-1 and regulates proliferation through PAK2.

Liver Zonation Disruption Fuels Hepatocellular Carcinoma in Chronic Liver Disease

This study identifies zonation disruption, specifically aberrant β-catenin expansion, as a novel driver of hepatocellular carcinoma in chronic liver disease, revealing a distinct human HCC subtype with therapeutic implications.

β-Catenin condensation facilitates clustering of the cadherin/catenin complex and formation of nascent cell-cell junctions

This study shows that β-catenin condensation drives the clustering of the cadherin/catenin complex and the formation of new cell-cell junctions.

The Actin regulator Mena promotes Wnt signalosome endocytosis and Wnt signalling.

This study identifies Mena as a key mediator of Wnt signalosome endocytosis, showing it promotes Wnt signaling by binding LRP5/6 and facilitating receptor uptake.

The emerging role of receptor trafficking in signalosome formation and sustained long-term Wnt/β-catenin signaling

The paper develops a mechanistic model to resolve debates on how receptor trafficking and membrane organization influence Wnt/β-catenin signaling, revealing a compensatory recycling mechanism and the role of ordered domains in signalosome stability.

Structural basis for Porcupine inhibition

This paper presents cryo-EM structures of PORCN with inhibitors, revealing a conserved water-mediated binding mechanism for rational drug design.

Lgr5+ Stem Cells Maintain Apex Position in Cell Hierarchy of the Intestinal Epithelium During Homeostasis and Injury

This study shows Lgr5+ stem cells maintain intestinal epithelial homeostasis and drive regeneration after injury through WNT signaling.

Differential Wnt/β-Catenin Signaling via TCF7L2/LEF1 Binding Specificity Shapes Cellular and Tumor Phenotypes

The paper identifies how differential TCF7L2/LEF1 binding specificity of {beta}-catenin shapes distinct gene regulatory outcomes in liver tumors.

The Wnt/APC destruction complex targets SREBP2 in a β-catenin-independent pathway to control cholesterol metabolism

This study identifies SREBP2 as a direct APC-AXIN1 substrate degraded via a β-catenin-independent pathway, regulating cholesterol metabolism and providing a target for APC-mutant colorectal cancer.

Deciphering the Interaction Between Dvl2 and Profilin2: Effector Molecules of Non-Canonical Wnt Signaling

This study identifies a novel interaction between Dvl2 and profilin2, revealing that profilin2 binds to the extreme-C-terminus of Dvl2 independently of the PDZ or DEP domains and remains active even when Dvl2 is autoinhibited.

WNK kinase regulates plasma membrane levels of the WNT inhibitor RNF43

This study identifies WNK kinases as regulators of RNF43, showing they control RNF43 membrane levels and WNT signaling, with implications for cancer therapy.

Leveraging WNT Hyperactivation to Kill Colorectal Cancer While Rejuvenating Healthy Intestine.

This paper identifies a therapeutic strategy using WNT hyperactivation to kill colorectal cancer cells while rejuvenating healthy intestinal tissue.

ETEC heat-labile toxin promotes β-catenin stabilization and transcriptional reprogramming to disrupt intestinal epithelial differentiation

This study shows ETEC heat-labile toxin stabilizes β-catenin and alters intestinal epithelial differentiation, leading to impaired nutrient absorption and growth issues.

Secreted Frizzled-Related Protein 1a regulates hematopoietic development in a dose-dependent manner

The paper shows Sfrp1a regulates zebrafish HSPC development and differentiation in a dose-dependent manner, with loss or gain of function affecting HSPC numbers and lineage differentiation.

Structural basis for regulation of Frizzled-4 signaling by the co-receptor Tetraspanin-12

This paper reports the structure of the FZD4-Tspan12 complex and shows how Tspan12 enhances Norrin signaling by facilitating trafficking and higher-affinity Norrin binding.

Targeting tankyrase scaffolding in the β-catenin destruction complex by PROTAC overcomes the limitation of catalytic inhibitors in cancer

This study shows that degrading tankyrase (TNKS) with PROTACs overcomes the limitations of catalytic inhibitors by preventing AXIN puncta formation and enhancing WNT/β-catenin pathway suppression in colorectal cancer.

The E3 Ubiquitin Ligase Trip12 attenuates Wnt9a/Fzd9b signaling during hematopoietic stem cell development

The paper identifies Trip12 as an E3 ubiquitin ligase that ubiquitinates Fzd9b, reducing its availability and Wnt9a/Fzd9b signaling in zebrafish hematopoietic stem cells.

A Wnt-induced conformational phospho-switch in DVL3 controls interaction with Frizzled receptors and Wnt/β-catenin signaling

The paper identifies a Wnt-induced phospho-switch in DVL3 that regulates its interaction with Frizzled receptors and Wnt/β-catenin signaling through conformational changes.

NEK9 ablation rewires docetaxel resistance through induction of ERK-mediated cancer cell pyroptosis

This study identifies NEK9 as a driver of docetaxel resistance in cancers and shows that its ablation sensitizes cells to docetaxel via ERK-mediated pyroptosis, suggesting fostamatinib as a potential therapeutic partner.

Loss of WNT2B Increases Progression from Dysplasia to Colorectal Cancer

This study shows that loss of WNT2B promotes colorectal cancer progression in mouse models and is associated with poor patient survival in human samples.

Wnt target IQGAP3 promotes Wnt signaling via disrupting Axin1-CK1α interaction.

This study identifies IQGAP3 as a Wnt signaling mediator that stabilizes β-catenin by disrupting Axin1-CK1α interaction and is itself regulated by Wnt signaling.

Pathogenic DVL frameshifting variants in Robinow syndrome disrupt WNT signaling and cellular dynamics

The paper investigates how pathogenic DVL frameshifting variants in Robinow syndrome disrupt WNT signaling and cellular dynamics by altering protein structure and function.

De Novo design of a potent Wnt Surrogate specific for the frizzled7 subtype members

This paper designs a potent Wnt surrogate specific for Fzd7 subtype members, showing strong binding affinity and functional activity in organoid formation and hair regeneration.

A pivotal role for Wnt antagonists in constraining Wnt activity to promote digit joint specification.

The paper shows that Wnt antagonists, working with Fgfs, prevent premature pSmad1/5 accumulation to maintain mesenchymal plasticity and balance digit phalanx and joint formation.

A Robust Crystallographic Platform for High-Throughput β-Catenin Ligand Discovery

This paper develops a robust crystallographic platform for discovering β-catenin ligands through optimized protein production and screening methods.

Secretion and signaling properties of Wnt11 and Wnt3 are determined by their N-terminus

This study shows that the N-terminus of Wnt proteins determines their secretion and signaling properties, with Wnt11's N-terminus enabling Evi/Wls-independent secretion and Frizzled 6 activation.