Document Detail


The redox protein HMGB1 regulates cell death and survival in cancer treatment.
MedLine Citation:
PMID:  20861675     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Daolin Tang; Michael T Loze; Herbert J Zeh; Rui Kang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Autophagy     Volume:  6     ISSN:  1554-8635     ISO Abbreviation:  Autophagy     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-30     Completed Date:  2011-03-02     Revised Date:  2011-06-30    
Medline Journal Info:
Nlm Unique ID:  101265188     Medline TA:  Autophagy     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1181-3     Citation Subset:  IM    
Affiliation:
The DAMP Laboratory, Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA. tangd2@upmc.edu
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology,  therapeutic use
Autophagy / drug effects
Cell Death / drug effects
Cell Survival / drug effects
HCT116 Cells
HMGB1 Protein / metabolism*
Humans
Models, Biological
Neoplasms / drug therapy*,  pathology*,  radiotherapy
Oxidation-Reduction / drug effects
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/HMGB1 Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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