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

•Autophagy is an emerging anticancer therapy target.•ATG4B inhibitors are being developed as a novel class of autophagy inhibitors.•ATG4B plays a cancer type-, treatment-, and context-dependent role.•Predictive markers will be instrumental to clinically develop ATG4B inhibitors. ATG4B belongs to the...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2013-11, Vol.441 (4), p.726-731
Main Authors: Tran, Elisa, Chow, Annabelle, Goda, Takeshi, Wong, Amy, Blakely, Kim, Rocha, Michelle, Taeb, Samira, Hoang, Van C., Liu, Stanley K., Emmenegger, Urban
Format: Article
Language:English
Subjects:
Animals
ATG4B
Autophagy
Autophagy - drug effects
Autophagy-Related Proteins
Cell Line, Tumor
Chemotherapy
Cysteine Endopeptidases - genetics
Cysteine Endopeptidases - metabolism
Cysteine Proteinase Inhibitors - pharmacology
Cysteine Proteinase Inhibitors - therapeutic use
Doxorubicin - pharmacology
Doxorubicin - therapeutic use
Drug Resistance, Neoplasm
Humans
Male
Mice
Mice, Nude
Molecular Targeted Therapy
Neoplasm Transplantation
Prostate cancer
Prostatic Neoplasms - drug therapy
Radiation therapy
Radiation Tolerance
Taxoids - pharmacology
Taxoids - therapeutic use
Topotecan - pharmacology
Topotecan - therapeutic use
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Summary:•Autophagy is an emerging anticancer therapy target.•ATG4B inhibitors are being developed as a novel class of autophagy inhibitors.•ATG4B plays a cancer type-, treatment-, and context-dependent role.•Predictive markers will be instrumental to clinically develop ATG4B inhibitors. 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 ATG4BC74Ain vitro and in vivo, we show that the effects of ATG4BC74A are cell type, treatment, and context-dependent. ATG4BC74A 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2013.10.117