title: Targeting Hsp70: A possible therapy for cancer.
abstract: In all organisms, heat-shock proteins (HSPs) provide an ancient defense system. These proteins act as molecular chaperones by assisting proper folding and refolding of misfolded proteins and aid in the elimination of old and damaged cells. HSPs include Hsp100, Hsp90, Hsp70, Hsp40, and small HSPs. Through its substrate-binding domains, Hsp70 interacts with wide spectrum of molecules, ranging from unfolded to natively folded and aggregated proteins, and provides cytoprotective role against various cellular stresses. Under pathophysiological conditions, the high expression of Hsp70 allows cells to survive with lethal injuries. Increased Hsp70, by interacting at several points on apoptotic signaling pathways, leads to inhibition of apoptosis. Elevated expression of Hsp70 in cancer cells may be responsible for tumorigenesis and for tumor progression by providing resistance to chemotherapy. In contrast, inhibition or knockdown of Hsp70 reduces the size of tumors and can cause their complete regression. Moreover, extracellular Hsp70 acts as an immunogen that participates in cross presentation of MHC-I molecules. The goals of this review are to examine the roles of Hsp70 in cancer and to present strategies targeting Hsp70 in the development of cancer therapeutics.
authors.affiliation: Cancer Biology Research and Training Program, Department of Biological Sciences, Alabama State University, AL 36101, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Cancer Biology Research and Training Program, Department of Biological Sciences, Alabama State University, AL 36101, USA.
authors.forename: James
authors.initials: J
authors.lastname: Stokes
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Udai P
authors.initials: UP
authors.lastname: Singh
authors.affiliation: Cancer Biology Research and Training Program, Department of Biological Sciences, Alabama State University, AL 36101, USA.
authors.forename: Karyn
authors.initials: K
authors.lastname: Scissum Gunn
authors.affiliation: Centre of Advance Study in Zoology, Faculty of Science, Banaras Hindu University, Varanasi 221 005, India.
authors.forename: Arbind
authors.initials: A
authors.lastname: Acharya
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Upender
authors.initials: U
authors.lastname: Manne
authors.affiliation: Cancer Biology Research and Training Program, Department of Biological Sciences, Alabama State University, AL 36101, USA. Electronic address: mmishra@alasu.edu.
authors.forename: Manoj
authors.initials: M
authors.lastname: Mishra
mesh_terms: D000818:Animals; D055785:Gene Knockdown Techniques; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*
chemical_list: D018840:HSP70 Heat-Shock Proteins
keywords: Apoptosis; Cancer therapeutics; Hsp70; Immunogenicity