Hsp70: A Cancer Target Inside and Outside the Cell

• Published in: Methods in molecular biology (Clifton, N.J.) Vol. 1709; p. 371
• Main Authors: Boudesco, Christophe, Cause, Sebastien, Jego, Gaëtan, Garrido, Carmen
• Format: Journal Article
• Language: English
• Published: United States 2018
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; HSP70 Heat-Shock Proteins - antagonists & inhibitors; HSP70 Heat-Shock Proteins - immunology; Humans; Immunotherapy - methods; Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - immunology; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - therapy; Immunomodulator; Hsp70; Anti-cancer therapy; Apoptosis; Cancer
• ISSN: 1940-6029
• DOI: 10.1007/978-1-4939-7477-1_27

Heat shock protein 70 (Hsp70) is the most ubiquitous stress-inducible chaperone. It accumulates in the cells in response to a wide variety of physiological and environmental insults including anticancer chemotherapy, thus allowing the cell to survive to lethal conditions. Intracellular Hsp70 is viewed as a cytoprotective protein. Indeed, this protein can inhibit key effectors of the apoptotic and autophagy machineries. 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 can even cause their complete involution. However, HSP70 is also found in the extra-cellular space where it may signal via membrane receptors or endosomes to alter gene transcription and cellular function. Overall, Hsp70 extracellular function is believed to be immnunogenic and the term chaperokine to define the extracellular chaperones such as Hsp70 has been advanced. In this chapter the knowledge to date, as well as some emerging paradigms about the intra- and extra-cellular functions of Hsp70, are presented. The strategies targeting Hsp70 that are being developed in cancer therapy will also be discussed.