Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 99, Issue 6, Pages 3627-3632Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.062698499
Keywords
p14 Arf; apoptosis; cancer; extracellular matrix
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Funding
- NCI NIH HHS [R29 CA74230] Funding Source: Medline
- NHLBI NIH HHS [P01 HL48728] Funding Source: Medline
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p53 mediates apoptosis of cells after DNA damage including tumor cells after radiation or chemotherapy. Survival of isolated cancer cells after therapy leads to recurrence of therapy-resistant tumors. We now show that for some melanoma, sarcoma, or fibroblastic cell types that survive without integrin-mediated adhesion, apoptosis in response to DNA damage requires cell adhesion. This effect correlates with rapid changes in levels of p14/p19 Arf and its downstream component, p53. Killing of nonadherent cells is increased by treatment with antiintegrin antibodies or by increasing levels of p53 or Arf. Consistent with low p53 levels, suspended cells show chromosomal instability after irradiation. Thus, loss of normal adhesion in susceptible tumor cells during genotoxic stress may play a role in therapy resistance and promote survival of cells with aberrant DNA.
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