Hsp70: Anti-apoptotic and Tumorigenic Protein

Abstract

Heat shock protein 70 (Hsp70) is a powerful chaperone whose expression is induced in response to a wide variety of physiological and environmental insults, including anticancer chemotherapy, thus allowing the cell to survive to lethal conditions. Hsp70 cytoprotective properties may be explained by its anti-apoptotic function. Indeed, this protein can inhibit key effectors of the apoptotic machinery at the pre- and postmitochondrial level. In cancer cells, the expression of Hsp70 is abnormally high, and Hsp70 may participate in oncogenesis and in resistance to chemotherapy. In rodent models, Hsp70 overexpression increases tumor growth and metastatic potential. Depletion or inhibition of Hsp70 frequently reduces the size of the tumors and even can cause their complete involution. But Hsp70 can also be found in the extracellular medium. Its role is then immunogenic and the term chaperokine to define the extracellular chaperones has been advanced. Hsp70 tumorigenic functions as well as the strategies that are being developed in cancer therapy in order to inhibit Hsp70 are commented in this chapter.

Binding of Human Nucleotide Exchange Factors to Heat Shock Protein 70 (Hsp70) Generates Functionally Distinct Complexes in Vitro

“…Accordingly, Hsp70 has become an attractive drug target for neurodegenerative and hyperproliferative disorders (3,4). However, it is difficult to envision strategies for selectively inhibiting its pathobiology without impacting its essential roles (5,6). To help guide this process, there is an interest in better understanding how Hsp70 is recruited into its various functions.…”

Anticancer Activity of Lichen Metabolites and Their Mechanisms at the Molecular Level

“…In addition, Russo et al (2012) reported that vicanicin and protolichesterinic acid significantly increased the expression of TNF-related apoptosis-inducing ligand (TRAIL) in LNCaP prostate cancer cells. The possibility of Hsp70 involvement in induction of intrinsic pathway-mediated apoptosis by vicanicin and protolichesterinic acid was also raised in this report since Hsp70 can inhibit key effectors of the apoptotic machinery at the mitochondria (Rerole et al 2011). As an intrinsic apoptosis pathway, Backorova et al (2012) reported that usnic acid and atranorin induced massive loss of mitochondrial membrane potential and activated programmed cell death in an ovarian cancer cell line (A2780) and colon cancer cell line (HT-29).…”

Triptolide reduces the viability of osteosarcoma cells by reducing MKP-1 and Hsp70 expression

“…Changes in Hsp expression levels are often regulated in the transcriptional steps (20). Hsp70 upregulation has been detected in patients with certain types of cancers, and therefore it is speculated that Hsp70 may contribute to resistance to chemotherapy (20).…”

“…Changes in Hsp expression levels are often regulated in the transcriptional steps (20). Hsp70 upregulation has been detected in patients with certain types of cancers, and therefore it is speculated that Hsp70 may contribute to resistance to chemotherapy (20). Inhibition of Hsp70 induction was previously used as a method to benefit the anti-leukemia activity of the Hsp90 inhibitor, 17-allylaminodemethoxy geldanamycin (21).…”