title: Context-dependent role of ATG4B as target for autophagy inhibition in prostate cancer therapy.
abstract: 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.
authors.affiliation: Biological Sciences, Sunnybrook Research Institute, Canada.
authors.forename: Elisa
authors.initials: E
authors.lastname: Tran
authors.forename: Annabelle
authors.initials: A
authors.lastname: Chow
authors.forename: Takeshi
authors.initials: T
authors.lastname: Goda
authors.forename: Amy
authors.initials: A
authors.lastname: Wong
authors.forename: Kim
authors.initials: K
authors.lastname: Blakely
authors.forename: Michelle
authors.initials: M
authors.lastname: Rocha
authors.forename: Samira
authors.initials: S
authors.lastname: Taeb
authors.forename: Van C
authors.initials: VC
authors.lastname: Hoang
authors.forename: Stanley K
authors.initials: SK
authors.lastname: Liu
authors.forename: Urban
authors.initials: U
authors.lastname: Emmenegger
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D000071183:Autophagy-Related Proteins; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011836:Radiation Tolerance; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D019772:Topotecan / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000071183:Autophagy-Related Proteins; D015853:Cysteine Proteinase Inhibitors; D043823:Taxoids; D000077143:Docetaxel; D019772:Topotecan; D004317:Doxorubicin; C507524:ATG4B protein, human; D003546:Cysteine Endopeptidases
keywords: ATG4B; Autophagy; Chemotherapy; Prostate cancer; Radiation therapy