Autophagy regulates selective HMGB1 release in tumor cells that are destined to die

J. Thorburn, H. Horita, J. Redzic, K. Hansen, A. E. Frankel, A. Thorburn

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Macroautophagy (hereafter referred to as autophagy) can increase or decrease the amount of cell death in response to various stimuli. To test whether autophagy also controls the characteristics associated with dying cells, we studied tumor cell killing by epidermal growth factor receptor-targeted diphtheria toxin (DT-EGF). DT-EGF kills epithelial and glioblastoma tumor cells with similar efficiency but by different mechanisms that depend on whether the cells activate autophagy when treated with the drug. Dying cells in which autophagy is induced selectively release the immune modulator high-mobility group B1 (HMGB1) without causing lysis of the cell membrane and classical necrosis. Conversely, cells that are killed by DT-EGF where autophagy is blocked, activate caspases but retain HMGB1. These data suggest that it may be feasible to manipulate the immunogenicity of dying cells by increasing or decreasing autophagy.

Original languageEnglish (US)
Pages (from-to)175-183
Number of pages9
JournalCell Death and Differentiation
Volume16
Issue number1
DOIs
StatePublished - 2009

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Autophagy
Neoplasms
Epidermal Growth Factor
Diphtheria Toxin
Immunotoxins
Glioblastoma
Caspases
Epidermal Growth Factor Receptor
Cell Death
Necrosis
Cell Membrane
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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Autophagy regulates selective HMGB1 release in tumor cells that are destined to die. / Thorburn, J.; Horita, H.; Redzic, J.; Hansen, K.; Frankel, A. E.; Thorburn, A.

In: Cell Death and Differentiation, Vol. 16, No. 1, 2009, p. 175-183.

Research output: Contribution to journalArticle

Thorburn, J. ; Horita, H. ; Redzic, J. ; Hansen, K. ; Frankel, A. E. ; Thorburn, A. / Autophagy regulates selective HMGB1 release in tumor cells that are destined to die. In: Cell Death and Differentiation. 2009 ; Vol. 16, No. 1. pp. 175-183.
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