Heat shock proteins in hematopoietic malignancies.
Inducible heat shock proteins are molecular chaperones whose expression is increased after many different types of stress. They have a protective function helping the cell to cope with lethal conditions. Their basal expression is low in nonstressed, normal and nontransformed cells. However, in cancer cells and particularly in hematological malignancies, they are surprisingly abundant. Malignant cells have to rewire their metabolic requirements and therefore have a higher need for chaperones. This cancer cell addiction for HSPs is the basis for the use of HSP inhibitors in cancer therapy. HSPs have been shown to interact with different key apoptotic proteins. As a result, HSPs can essentially block the apoptotic pathways at several steps, most of them involving the activation of cystein proteases called caspases. Apoptosis and differentiation are physiological processes that share many common features, for instance, a controlled caspase activation and chromatin condensation are frequently observed. It is, therefore, not surprising that HSPs may be implicated in the differentiation process. HSPs may determine the fate of the cells by orchestrating the decision of apoptosis versus differentiation. This review will focus on the role of HSPs in hematological malignancies and the emerging therapeutic options that are being either proposed or used to target these protective proteins.
Inserm, UMR866, Faculty of Medicine, 7 Boulevard Jeanne D'Arc, F-21000 Dijon, France.
Hajare
H
Mjahed
François
F
Girodon
Michaela
M
Fontenay
Carmen
C
Garrido
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008954:Models, Biological; D018832:Molecular Chaperones; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins