Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy

Qian Huang, Fang Li, Xinjian Liu, Wenrong Li, Wei Shi, Fei Fei Liu, Brian O'Sullivan, Zhimin He, Yuanlin Peng, Aik-Choon Tan, Ling Zhou, Jingping Shen, Gangwen Han, Xiao Jing Wang, Jackie Thorburn, Andrew Thorburn, Antonio Jimeno, David Raben, Joel S. Bedford, Chuan Yuan Li

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425 Citations (Scopus)

Abstract

In cancer treatment, apoptosis is a well-recognized cell death mechanism through which cytotoxic agents kill tumor cells. Here we report that dying tumor cells use the apoptotic process to generate potent growth-stimulating signals to stimulate the repopulation of tumors undergoing radiotherapy. Furthermore, activated caspase 3, a key executioner in apoptosis, is involved in the growth stimulation. One downstream effector that caspase 3 regulates is prostaglandin E 2 (PGE 2), which can potently stimulate growth of surviving tumor cells. Deficiency of caspase 3 either in tumor cells or in tumor stroma caused substantial tumor sensitivity to radiotherapy in xenograft or mouse tumors. In human subjects with cancer, higher amounts of activated caspase 3 in tumor tissues are correlated with markedly increased rate of recurrence and death. We propose the existence of a cell death-induced tumor repopulation pathway in which caspase 3 has a major role.

Original languageEnglish
Pages (from-to)860-866
Number of pages7
JournalNature Medicine
Volume17
Issue number7
DOIs
Publication statusPublished - 2011 Jul 1
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Huang, Q., Li, F., Liu, X., Li, W., Shi, W., Liu, F. F., O'Sullivan, B., He, Z., Peng, Y., Tan, A-C., Zhou, L., Shen, J., Han, G., Wang, X. J., Thorburn, J., Thorburn, A., Jimeno, A., Raben, D., Bedford, J. S., & Li, C. Y. (2011). Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nature Medicine, 17(7), 860-866. https://doi.org/10.1038/nm.2385