Cell–matrix and cell–cell adhesion are recognized physiological determinants of cell growth and survival. In epithelial and endothelial cell systems, oncogenic transformation has in several cases been shown to confer resistance to apoptosis upon depriving cells of substrate adhesion. We examined the effects of oncogenic transformation in adherent versus adhesion- deprived primary embryonic fibroblasts. Whereas untransformed early passage fibroblasts undergo cell cycle arrest, their Myc/Ras- or E1A/Ras-transformed counterparts rapidly enter apoptosis when placed into suspension. This phenomenon also occurs upon incubation with a soluble, RGD-containing integrin ligand and is blocked by a peptide antagonist to ICE family proteases or by aggregation of cells plated at high density. Loss of wild-type p53 modulates the kinetics but does not abrogate this death pathway. Transformation with activated Src rather than Ras rendered fibroblasts selectively resistant to adhesion-dependent apoptosis, an effect likely related to Src's role in integrin signaling, while simultaneously sensitizing the cells to radiation-induced apoptosis. Thus cell adhesion events regulate transformation-selective apoptosis in fibroblasts and provide potentially important targets for understanding and interfering with tumor cell viability.
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25 August 1997
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August 25 1997
Loss of Matrix Adhesion Triggers Rapid Transformation-Selective Apoptosis in Fibroblasts
Gaël McGill,
Gaël McGill
*Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and ‡Department of Biology, Swarthmore College, Swarthmore, Pennsylvania 19081
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Akiko Shimamura,
Akiko Shimamura
*Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and ‡Department of Biology, Swarthmore College, Swarthmore, Pennsylvania 19081
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Richard C. Bates,
Richard C. Bates
*Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and ‡Department of Biology, Swarthmore College, Swarthmore, Pennsylvania 19081
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Robert E. Savage,
Robert E. Savage
*Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and ‡Department of Biology, Swarthmore College, Swarthmore, Pennsylvania 19081
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David E. Fisher
David E. Fisher
*Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and ‡Department of Biology, Swarthmore College, Swarthmore, Pennsylvania 19081
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Gaël McGill
*Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and ‡Department of Biology, Swarthmore College, Swarthmore, Pennsylvania 19081
Akiko Shimamura
*Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and ‡Department of Biology, Swarthmore College, Swarthmore, Pennsylvania 19081
Richard C. Bates
*Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and ‡Department of Biology, Swarthmore College, Swarthmore, Pennsylvania 19081
Robert E. Savage
*Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and ‡Department of Biology, Swarthmore College, Swarthmore, Pennsylvania 19081
David E. Fisher
*Division of Pediatric Hematology/Oncology, Dana Farber Cancer Institute and Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and ‡Department of Biology, Swarthmore College, Swarthmore, Pennsylvania 19081
Please address all correspondence to David E. Fisher, Children's Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115. Tel.: (617) 632-4916; Fax: (617) 632-2085.
Received:
January 20 1997
Revision Received:
June 12 1997
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1997
J Cell Biol (1997) 138 (4): 901–911.
Article history
Received:
January 20 1997
Revision Received:
June 12 1997
Citation
Gaël McGill, Akiko Shimamura, Richard C. Bates, Robert E. Savage, David E. Fisher; Loss of Matrix Adhesion Triggers Rapid Transformation-Selective Apoptosis in Fibroblasts . J Cell Biol 25 August 1997; 138 (4): 901–911. doi: https://doi.org/10.1083/jcb.138.4.901
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