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.

Mjahed H ，Girodon F ，Fontenay M ，Garrido C ... -  《-》

Apoptosis versus cell differentiation: role of heat shock proteins HSP90, HSP70 and HSP27.

Lanneau D ，de Thonel A ，Maurel S ，Didelot C ，Garrido C ... -  《-》

Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy.

Schmitt E ，Gehrmann M ，Brunet M ，Multhoff G ，Garrido C ... -  《JOURNAL OF LEUKOCYTE BIOLOGY》

HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy (Review).

Wang X ，Chen M ，Zhou J ，Zhang X ... -  《-》

Targeting heat shock proteins in cancer.

Heat shock proteins (HSPs) HSP27, HSP70 and HSP90 are powerful chaperones. Their expression is induced in response to a wide variety of physiological and environmental insults including anti-cancer chemotherapy, thus allowing the cell to survive to lethal conditions. Different functions of HSPs have been described to account for their cytoprotective function, including their role as molecular chaperones as they play a central role in the correct folding of misfolded proteins, but also their anti-apoptotic properties. HSPs are often overexpressed in cancer cells and this constitutive expression is necessary for cancer cells' survival. HSPs may have oncogene-like functions and likewise mediate "non-oncogene addiction" of stressed tumor cells that must adapt to a hostile microenvironment, thereby becoming dependent for their survival on HSPs. HSP-targeting drugs have therefore emerged as potential anti-cancer agents. This review describes the different molecules and approaches being used or proposed in cancer therapy based on the in inhibition of HSP90, HSP70 and HSP27.

Jego G ，Hazoumé A ，Seigneuric R ，Garrido C ... -  《-》