Restoring the tumour mechanophenotype of vocal fold cancer reverts its malignant properties

Increased extracellular matrix deposition and stiffness promotes solid tumour progression. Yet, the precise mechanotransduction pathways, especially in less-studied mechanically responsive cancers, remain poorly understood. Here we address this gap using patient-derived tumour cells from early (mobile, T1) and advanced (immobile, T3) stages of vocal fold cancer, the most common squamous…

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Fast label-free live imaging with FlowVision reveals key principles of cancer cell arrest on endothelial monolayers

The rapid, transient, and unpredictable nature of interactions between circulating cells and the endothelium challenges the investigation of these events under flow conditions. Here, we developed an imaging and image-analysis framework called FlowVision, which integrates fast, bright-field live-cell imaging with deep-learning-based image analysis to quantitatively track cell landing and arrest…

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Calponin isoforms define the cell-type-specific organization and dynamics of actomyosin bundles

Contractile actomyosin bundles, stress fibers, are important for cell migration, adhesion, morphogenesis, and mechanosensing. Calponin (CNN) family proteins are abundant stress fiber components, but their cellular functions and isoform-specific roles remain poorly understood. By depleting the three CNN isoforms (calponin-1 [CNN1], calponin-2 [CNN2], and calponin-3 [CNN3]) individually and collectively from…

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2-hydroxyglutarate mediates whitening of brown adipocytes coupled to nuclear softening upon mitochondrial dysfunction

Mitochondria have a crucial role in regulating cellular homeostasis in response to intrinsic and extrinsic cues by changing cellular metabolism to meet these challenges. However, the molecular underpinnings of this regulation and the complete spectrum of these physiological outcomes remain largely unexplored. In this study, we elucidate the mechanisms driving…

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Integrin β1 activity controls colony morphology during human pluripotent stem cell state transitions

Integrin β1-mediated adhesion is dispensable in early mouse embryogenesis (pre-implantation) but indispensable post-implantation, suggesting distinct roles for β1-integrin-mediated adhesions in the naive (pre-implantation) versus primed (post-implantation) pluripotent stem cells (PSCs). We investigated the role of integrin β1 in regulating naive-like and primed human induced PSC (hiPSC) states. We find that…

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