Context-dependent role of ATG4B as target for autophagy inhibition in prostate cancer therapy

Biochem Biophys Res Commun. 2013 Nov 29;441(4):726-31. doi: 10.1016/j.bbrc.2013.10.117. Epub 2013 Oct 30.


ATG4B belongs to the autophagin family of cysteine proteases required for autophagy, an emerging target of cancer therapy. Developing pharmacological ATG4B inhibitors is a very active area of research. However, detailed studies on the role of ATG4B during anticancer therapy are lacking. By analyzing PC-3 and C4-2 prostate cancer cells overexpressing dominant negative ATG4B(C74A)in vitro and in vivo, we show that the effects of ATG4B(C74A) are cell type, treatment, and context-dependent. ATG4B(C74A) expression can either amplify the effects of cytotoxic therapies or contribute to treatment resistance. Thus, the successful clinical application of ATG4B inhibitors will depend on finding predictive markers of response.

Keywords: ATG4B; Autophagy; Chemotherapy; Prostate cancer; Radiation therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Autophagy-Related Proteins
  • Cell Line, Tumor
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Cysteine Proteinase Inhibitors / therapeutic use*
  • Docetaxel
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Molecular Targeted Therapy*
  • Neoplasm Transplantation
  • Prostatic Neoplasms / drug therapy*
  • Radiation Tolerance
  • Taxoids / pharmacology
  • Taxoids / therapeutic use
  • Topotecan / pharmacology
  • Topotecan / therapeutic use


  • Autophagy-Related Proteins
  • Cysteine Proteinase Inhibitors
  • Taxoids
  • Docetaxel
  • Topotecan
  • Doxorubicin
  • ATG4B protein, human
  • Cysteine Endopeptidases