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Mechanical force modulates global gene expression and beta-catenin signaling in colon cancer cells
Journal article   Open access   Peer reviewed

Mechanical force modulates global gene expression and beta-catenin signaling in colon cancer cells

Christopher L Avvisato, Xiang Yang, Salim Shah, Becky Hoxter, Weiqun Li, Richard Gaynor, Richard Pestell, Aydin Tozeren and Stephen W Byers
Journal of cell science, v 120(Pt 15), pp 2672-2682
01 Aug 2007
DOI: https://doi.org/10.1242/jcs.03476
PMID: 17635998
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1242/jcs.03476View
Published, Version of Record (VoR) Open

Abstract

Colonic Neoplasms - genetics Signal Transduction Humans Gene Expression Regulation, Neoplastic Stress, Mechanical JNK Mitogen-Activated Protein Kinases - metabolism NF-kappa B - metabolism Phosphatidylinositol 3-Kinases - metabolism Wnt Proteins - metabolism beta Catenin - metabolism Colonic Neoplasms - metabolism Fibronectins - metabolism Metabolic Networks and Pathways Cell Line, Tumor p38 Mitogen-Activated Protein Kinases - metabolism Laminin - metabolism rac1 GTP-Binding Protein - metabolism
At various stages during embryogenesis and cancer cells are exposed to tension, compression and shear stress; forces that can regulate cell proliferation and differentiation. In the present study, we show that shear stress blocks cell cycle progression in colon cancer cells and regulates the expression of genes linked to the Wnt/beta-catenin, mitogen-activated protein kinase (MAPK) and NFkappaB pathways. The shear stress-induced increase of the secreted Wnt inhibitor DKK1 requires p38 and activation of NFkappaB requires IkappaB kinase-beta. Activation of beta-catenin, important in Wnt signaling and the cause of most colon cancers, is inhibited by shear stress through a pathway involving laminin-5, alpha6beta4 integrin, phosphoinositide 3-kinase (PI 3-kinase) and Rac1 coupled with changes in the distribution of dephosphorylated beta-catenin. These data show that colon cancer cells respond to fluid shear stress by activation of specific signal transduction pathways and genetic regulatory circuits to affect cell proliferation, and indicate that the response of colon cancers to mechanical forces such as fluid shear stress should be taken into account in the management of the disease.

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106 citations in Web of Science
109 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
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