Mechanical Control of Epithelial-to-Mesenchymal Transitions in Development and Cancer.
Mechanical force modulates development, influences tissue homeostasis, and contributes to disease. Forces sculpt tissue-level behaviors and direct cell fate by engaging mechanoreceptors and by altering organization of the cytoskeleton and actomyosin contractility to stimulate mechanotransduction mechanisms that alter transcription. Nevertheless, how force specifically leverages mechanotransduction pathways to control transcriptional regulation of cell fate remains unclear. Here we review recent findings specifically in the context of epithelial-to-mesenchymal transitions that have revealed conserved mechanisms whereby extracellular force, mediated through cell-extracellular matrix and cell-cell junctional complexes, induces transcriptional reprogramming to alter cell and tissue fate. We focus on the interplay between tissue mechanics and the epithelial-to-mesenchymal transitions that occur during embryonic development and cancer malignancy. We describe the adhesion-linked cellular machinery that mediates mechano-transduction and elaborate on how these force-linked networks stimulate key transcriptional programs that induce an epithelial-to-mesenchymal phenotypic transition, thereby providing an overview of how mechanical signals can be translated into a change in cell fate.
Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, California 94143; email: Valerie.Weaver@ucsf.edu.
Laralynne
L
Przybyla
Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, California 94143; email: Valerie.Weaver@ucsf.edu.|Joint Graduate Group in Bioengineering (University of California, San Francisco, and University of California, Berkeley), San Francisco, California 94143.
Jonathon M
JM
Muncie
Center for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco, California 94143; email: Valerie.Weaver@ucsf.edu.|Departments of Anatomy, Bioengineering, and Therapeutic Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, The Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143.
Valerie M
VM
Weaver
D000818:Animals; D047108:Embryonic Development; D058750:Epithelial-Mesenchymal Transition; D025461:Feedback, Physiological; D006801:Humans; D040542:Mechanotransduction, Cellular; D009369:Neoplasms / Q000473:pathology*; D015398:Signal Transduction
cytoskeleton; mechanobiology; metastasis; microenvironment; stem cells; transcription