INTRODUCTIONTumour Necrosis Factor Receptor‐Associated Protein 1 (TRAP1) is a member of the HSP90 family with predominantly mitochondrial localization, whose cytoprotective role has been widely documented. Several studies suggest that TRAP1 preserves cellular function by protecting mitochondrial function, limiting the effects of oxidative stress either by decreasing reactive oxygen species (ROS)‐mediated oxidation or by attenuating ROS production and through preservation of the mitochondrial membrane potential by limiting mitochondrial permeability transition pore (mPTP) opening through its interaction with HSP90 and cyclophilin D (CypD). Recent studies identify additional cytoprotective roles for TRAP1 in cellular stress responses including the unfolded protein response to ER stress and autophagy. Together, these effects seem to contribute for TRAP1 protective effect against apoptosis. These anti‐apoptotic functions contribute to human oncogenesis. TRAP1 expression is increased in numerous human malignancies. Functionally, inhibition of mitochondrial TRAP1 and related chaperones is cytotoxic to tumour cells, but not normal cells. Anti‐apoptotic functions of TRAP1 confer tumour cells resistance against different chemotherapeutic agents. For these reasons, TRAP1 has been proposed as a potential biomarker and target for anticancer therapies. In this context, mitochondrial‐targeted agents have been developed to selectively inhibit HSP90‐like mitochondrial chaperones inducing cell death and reverting tumour cell multi‐drug‐resistant phenotype.It has
European Journal of Clinical Investigation – Wiley
Published: Jan 1, 2018
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