Activated checkpoint kinase 2 provides a survival signal for tumor cells

Jagadish C. Ghosh, Takehiko Dohi, Christopher M. Raskett, Timothy F. Kowalik, Dario C. Altieri

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Tumor cells often become resistant to DNA damage-based therapy; however, the underlying mechanisms are not yet understood. Here, we show that tumor cells exposed to DNA damage counteract cell death by releasing the antiapoptotic protein, survivin, from mitochondria. This is independent of p53, and requires activated checkpoint kinase 2 (Chk2), a putative tumor suppressor. Molecular or genetic targeting of Chk2 prevents the release of survivin from mitochondria, enhances DNA damage-induced tumor cell apoptosis, and inhibits the growth of resistant in vivo tumors. Therefore, activated Chk2 circumvents its own tumor-suppressive functions by promoting tumor cell survival. Inhibiting Chk2 in combination with DNA-damaging agents may provide a rational approach for treating resistant tumors.

Original languageEnglish (US)
Pages (from-to)11576-11579
Number of pages4
JournalCancer Research
Volume66
Issue number24
DOIs
StatePublished - Dec 15 2006

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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