title: The mechanical regulation of integrin-cadherin crosstalk organizes cells, signaling and forces.
abstract: Cadherins and integrins are intrinsically linked through the actin cytoskeleton and share common signaling molecules. Although mechanosensing by the integrin-actin axis has long been appreciated, a growing body of literature now demonstrates that cadherins also transduce and respond to mechanical forces. Mounting evidence shows that mechanically driven crosstalk between integrins and cadherins regulates the spatial distribution of these receptors, their signaling intermediates, the actin cytoskeleton and intracellular forces. This interplay between integrins and cadherins can control fibronectin matrix assembly and signaling, and a fine balance between traction forces at focal adhesions and intercellular tension at adherens junctions is crucial for directional collective cell migration. In this Commentary, we discuss two central ideas: (1) how the dynamic interplay between integrins and cadherins regulates the spatial organization of intracellular signals and the extracellular matrix, and (2) the emerging consensus that intracellular force is a central mechanism that dictates cell behavior, guides tissue development and ultimately drives physiology.
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Program in Translational Biomechanics, Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA kmui@mail.med.upenn.edu.
authors.forename: Keeley L
authors.initials: KL
authors.lastname: Mui
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Program in Translational Biomechanics, Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Assoian
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002477:Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015820:Cadherins; D016023:Integrins
keywords: Actin cytoskeleton; Adherens junction; Focal adhesion; Mechanotransduction