Dual role of heat shock proteins as regulators of apoptosis and innate immunity.
Stress or heat shock proteins (HSPs) 70 and 90 are powerful chaperones whose expression is induced in response to a wide variety of physiological and environmental insults. These proteins have different functions depending on their intracellular or extracellular location. Intracellular HSPs have a protective function. They allow the cells to survive potentially lethal conditions. The cytoprotective functions of HSPs can largely be explained by their anti-apoptotic properties. HSP70 and HSP90 can directly interact with different proteins of the tightly regulated programmed cell death machinery and thereby block the apoptotic process at distinct key points. In cancer cells, where the expression of HSP70 and/or HSP90 is frequently abnormally high, they participate in oncogenesis and in resistance to chemotherapy. Therefore, the inhibition of HSPs has become an interesting strategy in cancer therapy. In contrast to intracellular HSPs, extracellularly located or membrane-bound HSPs mediate immunological functions. They can elicit an immune response providing a link between innate and adaptive immune systems. In cancer, most immunotherapeutical approaches based on extracellular HSPs exploit their carrier function for immunogenic peptides. This review will focus on the roles of HSP70 and HSP90 in apoptosis and in innate immunity and how these functions are being exploited in cancer therapy.
Joly
Anne-Laure
AL
INSERM U866, Faculty of Medicine and Pharmacy, University of Dijon, Dijon, France.
Wettstein
Guillaume
G
Mignot
Gregoire
G
Ghiringhelli
François
F
Garrido
Carmen
C
D000276:Adjuvants, Immunologic; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D017209:Apoptosis; D019496:Cancer Vaccines; D002471:Cell Transformation, Neoplastic; D019610:Cytoprotection; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D010446:Peptide Fragments