The redox protein HMGB1 regulates cell death and survival in cancer treatment.
Metabolic and therapeutic stress activates several signal transduction pathways and releases damageassociated molecular pattern molecules (DAMPs) that regulate cell death and cell survival. The prototypical DAMP, high-mobility group box 1 protein (HMGB1) is released with sustained autophagy, late apoptosis and necrosis. Our recent findings reveal that the HMGB1 protein triggers autophagy or apoptosis in cancer cells, depending on its redox status. Reducible HMGB1 binds to the receptor for advanced glycation end products (RAGE), induces Beclin 1-dependent autophagy and promotes pancreatic or colon tumor cell line resistance to chemotherapeutic agents or ionizing radiation. In contrast, oxidized HMGB1 increases the cytotoxicity of these agents and induces apoptosis via the mitochondrial pathway. This suggests a new function for HMGB1 within the tumor microenvironment, regulating cell death and survival and suggests that it plays an important functional role in cross-regulating apoptosis and autophagy.
Tang
Daolin
D
The DAMP Laboratory, Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA. tangd2@upmc.edu
Loze
Michael T
MT
Zeh
Herbert J
HJ
Kang
Rui
R
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045325:HCT116 Cells; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000532:radiotherapy; D010084:Oxidation-Reduction / Q000187:drug effects
D000970:Antineoplastic Agents; D024243:HMGB1 Protein