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Transforming growth factor β regulates cell–cell adhesion through extracellular matrix remodeling and activation of focal adhesion kinase in human colon carcinoma Moser cells

Oncogene volume 23, pages 5558–5561 (2004)Cite this article

Abstract

Transforming growth factor (TGF) β is a potent regulator of cell–matrix and cell-cell adhesions (collectively termed cellular adhesions). Cellular adhesions play crucial roles in controlling the differentiation of epithelial cells and in maintaining the integrity of the epithelium. Loss of TGF β-responsiveness is thought to be an important early initiating event in the malignant progression of epithelial cancer. In the TGFβ-responsive human colon adenocarcinoma Moser cells, TGFβ promotes cellular adhesions and suppresses their malignant phenotype. TGFβ promotes cell–matrix adhesion by inducing the synthesis of extracellular matrix (ECM) adhesion molecules and the expression of integrin receptors for these molecules (termed ECM remodeling). TGFβ promotes cell–cell adhesion through the induction of E-cadherin expression, an epithelial associated homotypic cell–cell adhesion molecule, which also functions as a tumor suppressor in colon cancer. How TGFβ regulates E-cadherin expression is not known. In this study, we showed that the induction of E-cadherin by TGFβ was mediated through the activation of focal adhesion kinase (FAK), a major signaling molecule in focal adhesion contacts and that the activation of FAK was due to ECM remodeling and increased cell–matrix interactions. Thus, TGFβ regulates cell–cell adhesion through its ability to remodel the ECM and to activate FAK through ECM remodeling.

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Acknowledgements

This study was supported by Public Health Service Grant R01CA47775.

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Authors and Affiliations

  1. Division of Pathology and Laboratory Medicine, Department of Molecular Pathology, the University of Texas, MD Anderson Cancer Center, Houston, 77030, TX, USA

    Hongmei Wang, Venugopal Radjendirane & Subhas Chakrabarty

  2. Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, 77030, TX, USA

    Kishore K Wary

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  1. Hongmei Wang
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  2. Venugopal Radjendirane
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  4. Subhas Chakrabarty
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Correspondence to Subhas Chakrabarty.

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Wang, H., Radjendirane, V., Wary, K. et al. Transforming growth factor β regulates cell–cell adhesion through extracellular matrix remodeling and activation of focal adhesion kinase in human colon carcinoma Moser cells. Oncogene 23, 5558–5561 (2004). https://doi.org/10.1038/sj.onc.1207701

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