Disruption of epithelial cell-matrix interactions induces apoptosis

doi:10.1083/jcb.124.4.619

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Disruption of epithelial cell-matrix interactions induces apoptosis

SM Frisch and H Francis
La Jolla Cancer Research Foundation, California 92037.

Cell-matrix interactions have major effects upon phenotypic features such as gene regulation, cytoskeletal structure, differentiation, and aspects of cell growth control. Programmed cell death (apoptosis) is crucial for maintaining appropriate cell number and tissue organization. It was therefore of interest to determine whether cell- matrix interactions affect apoptosis. The present report demonstrates that apoptosis was induced by disruption of the interactions between normal epithelial cells and extracellular matrix. We have termed this phenomenon "anoikis." Overexpression of bcl-2 protected cells against anoikis. Cellular sensitivity to anoikis was apparently regulated: (a) anoikis did not occur in normal fibroblasts; (b) it was abrogated in epithelial cells by transformation with v-Ha-ras, v-src, or treatment with phorbol ester; (c) sensitivity to anoikis was conferred upon HT1080 cells or v-Ha-ras-transformed MDCK cells by reverse- transformation with adenovirus E1a; (d) anoikis in MDCK cells was alleviated by the motility factor, scatter factor. The results suggest that the circumvention of anoikis accompanies the acquisition of anchorage independence or cell motility.
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Isakoff, S. J., Engelman, J. A., Irie, H. Y., Luo, J., Brachmann, S. M., Pearline, R. V., Cantley, L. C., Brugge, J. S. (2005). Breast Cancer-Associated PIK3CA Mutations Are Oncogenic in Mammary Epithelial Cells. Cancer Res. 65: 10992-11000 [Abstract] [Full Text]
Samarel, A. M. (2005). Costameres, focal adhesions, and cardiomyocyte mechanotransduction. Am. J. Physiol. Heart Circ. Physiol. 289: H2291-H2301 [Abstract] [Full Text]
Arredondo, J., Chernyavsky, A. I., Karaouni, A., Grando, S. A. (2005). Novel Mechanisms of Target Cell Death and Survival and of Therapeutic Action of IVIg in Pemphigus. Am. J. Pathol. 167: 1531-1544 [Abstract] [Full Text]
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van Beurden, H.E., Von den Hoff, J.W., Torensma, R., Maltha, J.C., Kuijpers-Jagtman, A.M. (2005). Myofibroblasts in Palatal Wound Healing: Prospects for the Reduction of Wound Contraction after Cleft Palate Repair. JDR 84: 871-880 [Abstract] [Full Text]
Futter, C. E., Crowston, J. G., Allan, B. D. S. (2005). Interaction with Collagen IV Protects Lens Epithelial Cells from Fas-Dependent Apoptosis by Stimulating the Production of Soluble Survival Factors. IOVS 46: 3256-3262 [Abstract] [Full Text]
Stojanovic, M., Germain, M., Nguyen, M., Shore, G. C. (2005). BAP31 and Its Caspase Cleavage Product Regulate Cell Surface Expression of Tetraspanins and Integrin-mediated Cell Survival. J. Biol. Chem. 280: 30018-30024 [Abstract] [Full Text]
Aixinjueluo, W., Furukawa, K., Zhang, Q., Hamamura, K., Tokuda, N., Yoshida, S., Ueda, R., Furukawa, K. (2005). Mechanisms for the Apoptosis of Small Cell Lung Cancer Cells Induced by Anti-GD2 Monoclonal Antibodies: ROLES OF ANOIKIS. J. Biol. Chem. 280: 29828-29836 [Abstract] [Full Text]
Geiger, T. R., Peeper, D. S. (2005). The Neurotrophic Receptor TrkB in Anoikis Resistance and Metastasis: A Perspective. Cancer Res. 65: 7033-7036 [Abstract] [Full Text]
Mulero-Navarro, S., Pozo-Guisado, E., Perez-Mancera, P. A., Alvarez-Barrientos, A., Catalina-Fernandez, I., Hernandez-Nieto, E., Saenz-Santamaria, J., Martinez, N., Rojas, J. M., Sanchez-Garcia, I., Fernandez-Salguero, P. M. (2005). Immortalized Mouse Mammary Fibroblasts Lacking Dioxin Receptor Have Impaired Tumorigenicity in a Subcutaneous Mouse Xenograft Model. J. Biol. Chem. 280: 28731-28741 [Abstract] [Full Text]
Pachmann, K., Uhr, J. (2005). Longtime Recirculating Tumor Cells in Breast Cancer Patients. Clin. Cancer Res. 11: 5657-5658 [Full Text]
Fazal, F., Gu, L., Ihnatovych, I., Han, Y., Hu, W., Antic, N., Carreira, F., Blomquist, J. F., Hope, T. J., Ucker, D. S., de Lanerolle, P. (2005). Inhibiting Myosin Light Chain Kinase Induces Apoptosis In Vitro and In Vivo. Mol. Cell. Biol. 25: 6259-6266 [Abstract] [Full Text]