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

Research output: Contribution to journalArticle

402 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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Radiotherapy
Caspase 3
Tumors
Cells
Neoplasms
Cell death
Effector Caspases
Apoptosis
Cell Death
Growth
Oncology
Cytotoxins
Prostaglandins E
Heterografts
Tissue

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., ... 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

Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. / Huang, Qian; Li, Fang; Liu, Xinjian; Li, Wenrong; Shi, Wei; Liu, Fei Fei; O'Sullivan, Brian; He, Zhimin; Peng, Yuanlin; Tan, Aik-Choon; Zhou, Ling; Shen, Jingping; Han, Gangwen; Wang, Xiao Jing; Thorburn, Jackie; Thorburn, Andrew; Jimeno, Antonio; Raben, David; Bedford, Joel S.; Li, Chuan Yuan.

In: Nature Medicine, Vol. 17, No. 7, 01.07.2011, p. 860-866.

Research output: Contribution to journalArticle

Huang, Q, Li, F, Liu, X, Li, W, Shi, W, Liu, FF, O'Sullivan, B, He, Z, Peng, Y, Tan, A-C, Zhou, L, Shen, J, Han, G, Wang, XJ, Thorburn, J, Thorburn, A, Jimeno, A, Raben, D, Bedford, JS & Li, CY 2011, 'Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy', Nature Medicine, vol. 17, no. 7, pp. 860-866. https://doi.org/10.1038/nm.2385
Huang, Qian ; Li, Fang ; Liu, Xinjian ; Li, Wenrong ; Shi, Wei ; Liu, Fei Fei ; O'Sullivan, Brian ; He, Zhimin ; Peng, Yuanlin ; Tan, Aik-Choon ; Zhou, Ling ; Shen, Jingping ; Han, Gangwen ; Wang, Xiao Jing ; Thorburn, Jackie ; Thorburn, Andrew ; Jimeno, Antonio ; Raben, David ; Bedford, Joel S. ; Li, Chuan Yuan. / Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. In: Nature Medicine. 2011 ; Vol. 17, No. 7. pp. 860-866.
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