DAMP-mediated autophagy contributes to drug resistance

Liying Liu, Minghua Yang, Rui Kang, Zhuo Wang, Yiming Zhao, Yan Yu, Min Xie, Xiaocheng Yin, Kristen M. Livesey, Michael T. Lotze, Daolin Tang, Lizhi Cao

Research output: Contribution to journalShort survey

57 Scopus citations

Abstract

Damage-associated molecular pattern molecules (DAMPs) are cellularly derived molecules that can initiate and perpetuate immune responses following trauma, ischemia and other types of tissue damage in the absence of pathogenic infection. High mobility group box 1 (HMGB1) is a prototypical DAMP and is associated with the hallmarks of cancer. Recently we found that HMGB1 release after chemotherapy treatment is a critical regulator of autophagy and a potential drug target for therapeutic interventions in leukemia. Overexpression of HMGB1 by gene transfection rendered leukemia cells resistant to cell death; whereas depletion or inhibition of HMGB1 and autophagy by RNA interference or pharmacological inhibitors increased the sensitivity of leukemia cells to chemotherapeutic drugs. HMGB1 release sustains autophagy as assessed by microtubule-associated protein 1 light chain 3 (LC3) lipidation, redistribution of LC3 into cytoplasmic puncta, degradation of p62 and accumulation of autophagosomes and autolysosomes. Moreover, these data suggest a role for HMGB1 in the regulation of autophagy through the PI3KC3-MEK-ERK pathway, supporting the notion that HMGB1-induced autophagy promotes tumor resistance to chemotherapy.

Original languageEnglish (US)
Pages (from-to)112-114
Number of pages3
JournalAutophagy
Volume7
Issue number1
DOIs
StatePublished - Jan 2011
Externally publishedYes

Keywords

  • Autophagy
  • Chemotherapy resistance
  • DAMP
  • ERK
  • HMGB1
  • Leukemia
  • PI3KC3

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Liu, L., Yang, M., Kang, R., Wang, Z., Zhao, Y., Yu, Y., Xie, M., Yin, X., Livesey, K. M., Lotze, M. T., Tang, D., & Cao, L. (2011). DAMP-mediated autophagy contributes to drug resistance. Autophagy, 7(1), 112-114. https://doi.org/10.4161/auto.7.1.14005