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E-cadherin is a major cell-cell adhesion molecule involved in mechanotransduction at cell-cell contacts in tissues. Because epithelial cells respond to rigidity and tension in tissue through E-cadherin, there must be active processes that test and respond to the mechanical properties of these adhesive contacts. Using submicrometer, E-cadherin-coated polydimethylsiloxane pillars, we find that cells generate local contractions between E-cadherin adhesions and pull to a constant distance for a constant duration, irrespective of pillar rigidity. These cadherin contractions require nonmuscle myosin IIB, tropomyosin 2.1, α-catenin, and binding of vinculin to α-catenin. Cells spread to different areas on soft and rigid surfaces with contractions, but spread equally on soft and rigid without. We further observe that cadherin contractions enable cells to test myosin IIA-mediated tension of neighboring cells and sort out myosin IIA-depleted cells. Thus, we suggest that epithelial cells test and respond to the mechanical characteristics of neighboring cells through cadherin contractions.
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http://dx.doi.org/10.1126/sciadv.abk0387 | DOI Listing |
bioRxiv
June 2025
Biomedical Mass Spectrometry Center, University of Pittsburgh Schools of the Health Sciences, Pittsburgh, PA, USA.
Mechanical coupling and chemical communication between cardiomyocytes are facilitated through a specialized adhesive structure known as the intercalated disc (ICD). The ICD is essential for heart organization and contraction. Yet, the network of adhesion, adaptor, and signaling proteins that form the ICD remains poorly defined.
View Article and Find Full Text PDFDev Cell
July 2025
Laboratoire de Biologie du Développement - Institut de Biologie Paris Seine, UMR7622, Sorbonne Université, 7-9 quai Saint Bernard, 75005 Paris, France; Development and Stem Cell Program, IGBMC, UMR7104, U964, Université de Strasbourg, 1 rue Laurent Fries, BP10142, 67400 Illkirch, France. Electron
A key challenge in development is understanding how complex organisms physically coordinate the morphogenesis of multiple tissues. Here, using biophysical approaches, we investigate how muscles under the epidermis specifically stimulate the extension of anterior-posterior (AP)-oriented epidermal adherens junctions during late C. elegans embryonic elongation.
View Article and Find Full Text PDFTissue Cell
October 2025
Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, Imaging Platform, University of Florence, Largo Brambilla 3, Florence 50134, Italy. Electronic address:
Endothelial-to-mesenchymal transition (EndMT) is a key contributor to dermal fibrosis. The soluble form of the α-Klotho (sKL) hormone has been shown to counteract fibrotic processes in multiple organs, but its role in dermal fibrosis and EndMT remains unexplored. To investigate whether sKL may inhibit transforming growth factor β1 (TGFβ1)-induced EndMT in human dermal microvascular endothelial cells (H-dMVECs), cells pretreated with recombinant human sKL and subsequently stimulated with recombinant human TGFβ1 were assessed for morphological changes, gene and protein expression of both endothelial and mesenchymal/myofibroblast markers, and functional contractility through qPCR, Western blotting, immunofluorescence, and collagen gel contraction assays, respectively.
View Article and Find Full Text PDFAdv Sci (Weinh)
August 2025
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA.
FAT atypical cadherin 1 (FAT1) is one of the most frequently mutated genes in head and neck squamous cell carcinoma (HNSCC), exhibiting the highest mutation rate across different tumor types. Although FAT1's role has attracted considerable attention, its impact on cancer metabolism and treatment resistance remains poorly understood. In this study, it is demonstrated that knockout of mutant FAT1 in HNSCC cells attenuates CPT1A-driven fatty acid oxidation (FAO) through downregulation of the transcription factor ASCL2, leading to marked suppression of tumor growth.
View Article and Find Full Text PDFNeoplasia
June 2025
Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan. Electronic address:
Background: High-grade endometrial cancer (EC) has a poor prognosis, but molecular classification-based treatments present new therapeutic opportunities. Antibody-drug conjugates (ADC) emerge as promising tools, yet a deeper understanding of antigen dynamics, optimal therapeutic sequencing, and resistance mechanisms is essential. This study investigates the utility of patient-derived xenograft (PDX) models for EC as preclinical platforms, evaluating molecular subtypes and the ADC targets expression of patient and PDX tumors.
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