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Biology subjects

Manzato, C.

Publications and source records attributed to Manzato, C..

2 recordsLinked to original sources

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

Cadherin-based junctions establish dynamically regulated adhesion between cells to coordinate tissue integrity and morphogenetic movements. Adhesion strength can be modulated by the organization of individual cadherin complexes into lateral clusters. Here, we identify a novel clustering mechanism of the cadherin complex established by its core component {beta}-catenin. We show that the disordered termini of {beta}-catenin drive the formation of condensates that incorporate other components of the cadherin complex in vitro. Using {beta}-catenin mutants with hampered condensation, we demonstrate that {beta}-catenin condensation nucleates the formation of submicron cadherin/catenin clusters that further develop into stable sites of adhesion. Furthermore, we show that {beta}-catenin-dependent clustering ensures the efficient formation of de novo cell-cell adhesions. Our data thus indicate a role for {beta}-catenin condensates in the supramolecular organization of the cadherin complex, and reveal that the function of {beta}-catenin in the cadherin complex extends beyond connecting cadherin to -catenin and the actin cytoskeleton.

cell biology↗

Condensate screening identifies YM155 as β-catenin condensate inhibitor in colorectal cancer

{beta}-catenin is a transcriptional cofactor crucial in forming biomolecular condensates that drive WNT target gene transcription. Its pathological accumulation in the nucleus is a critical step in WNT-driven cancers, such as colorectal cancer. Disrupting {beta}-catenin condensates is a promising cancer treatment strategy, but no clinical applications currently exist. In this study, we developed a Nanobody Enabled Condensate Observation (NECO) screening platform to identify small molecules that modulate {beta}-catenin condensates. The platform revealed compounds that either enhanced or reduced {beta}-catenin transcriptional condensates. Among them, YM155 (sepantronium bromide) was identified as an inhibitor, disrupting essential weak interactions for condensate formation. This disruption effectively inhibits the proliferation of WNT-driven colorectal cancer organoids. These findings show that the NECO platform can identify small molecules that target {beta}-catenin condensates and suggest YM155 as a potential anti-cancer agent for colorectal cancer.

molecular biology↗