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  1. Free, publicly-accessible full text available April 1, 2024
  2. Raia Hadsell ; Kyunghyun Cho ; Hugo Larochelle (Ed.)
  3. In epithelia, breakdown of tensional homeostasis is closely associated with E-cadherin dysfunction and disruption of tissue function and integrity. In this study, we investigated the effect of E-cadherin mutations affecting distinct protein domains on tensional homeostasis of gastric cancer cells. We used micropattern traction microscopy to measure temporal fluctuations of cellular traction forces in AGS cells transfected with the wild-type E-cadherin or with variants affecting the extracellular, the juxtamembrane, and the intracellular domains of the protein. We focused on the dynamic aspect of tensional homeostasis, namely the ability of cells to maintain a consistent level of tension, with low temporal variability around a set point. Cells were cultured on hydrogels micropatterned with different extracellular matrix (ECM) proteins to test whether the ECM adhesion impacts cell behavior. A combination of Fibronectin and Vitronectin was used as a substrate that promotes the adhesive ability of E-cadherin dysfunctional cells, whereas Collagen VI was used to test an unfavorable ECM condition. Our results showed that mutations affecting distinct E-cadherin domains influenced differently cell tensional homeostasis, and pinpointed the juxtamembrane and intracellular regions of E-cadherin as the key players in this process. Furthermore, Fibronectin and Vitronectin might modulate cancer cell behavior towards tensional homeostasis. 
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  4. Abstract Background

    Tumour progression relies on the ability of cancer cells to penetrate and invade neighbouring tissues. E-cadherin loss is associated with increased cell invasion in gastric carcinoma, and germline mutations of the E-cadherin gene are causative of hereditary diffuse gastric cancer. Although E-cadherin dysfunction impacts cell–cell adhesion, cell dissemination also requires an imbalance of adhesion to the extracellular matrix (ECM).

    Methods

    To identify ECM components and receptors relevant for adhesion of E-cadherin dysfunctional cells, we implemented a novel ECM microarray platform coupled with molecular interaction networks. The functional role of putative candidates was determined by combining micropattern traction microscopy, protein modulation and in vivo approaches, as well as transcriptomic data of 262 gastric carcinoma samples, retrieved from the cancer genome atlas (TCGA).

    Results

    Here, we show that E-cadherin mutations induce an abnormal interplay of cells with specific components of the ECM, which encompasses increased traction forces and Integrin β1 activation. Integrin β1 synergizes with E-cadherin dysfunction, promoting cell scattering and invasion. The significance of the E-cadherin-Integrin β1 crosstalk was validated inDrosophilamodels and found to be consistent with evidence from human gastric carcinomas, where increased tumour grade and poor survival are associated with low E-cadherin and high Integrin β1 levels.

    Conclusions

    Integrin β1 is a key mediator of invasion in carcinomas with E-cadherin impairment and should be regarded as a biomarker of poor prognosis in gastric cancer.

     
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  5. null (Ed.)
  6. Abstract

    Optical lenses require feature resolution and surface roughness that are beyond most (3D) printing methods. A new continuous projection‐based vat photopolymerization process is reported that can directly shape polymer materials into optical lenses with microscale dimensional accuracy (< 14.7 µm) and nanoscale surface roughness (< 20 nm) without post‐processing. The main idea is to utilize frustum layer stacking, instead of the conventional 2.5D layer stacking, to eliminate staircase aliasing. A continuous change of mask images is achieved using a zooming‐focused projection system to generate the desired frustum layer stacking with controlled slant angles. The dynamic control of image size, objective and imaging distances, and light intensity involved in the zooming‐focused continuous vat photopolymerization are systematically investigated. The experimental results reveal the effectiveness of the proposed process. The 3D‐printed optical lenses with various designs, including parabolic lenses, fisheye lenses, and a laser beam expander, are fabricated with a surface roughness of 3.4 nm without post‐processing. The dimensional accuracy and optical performance of the 3D‐printed compound parabolic concentrators and fisheye lenses within a few millimeters are investiagted. These results highlight the rapid and precise nature of this novel manufacturing process, demonstrating a promising avenue for future optical component and device fabrication.

     
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