Targeting Hsp70: A possible therapy for cancer. Issue 1 (28th April 2016)

• Record Type: Journal Article
• Authors: Kumar, Sanjay; Stokes, James; Singh, Udai P.; Scissum Gunn, Karyn; Acharya, Arbind; Manne, Upender; Mishra, Manoj
• Is Part Of: Cancer letters. Volume 374:Issue 1(2016)
• Page Start: 156
• Page End: 166
• Publication Date: 2016-04-28
• Subjects: Hsp70 -- Apoptosis -- Cancer therapeutics -- Immunogenicity; HSPs Heat shock proteins -- Hsp70 Heat shock protein 70 -- Hsp75 Heat shock protein 75 -- Hsp100 Heat shock protein100 -- Hsp90 Heat shock protein 90 -- Hsp40 Heat shock protein 40 -- Hsp33 Heat shock protein 33 -- sHSPs Small Heat shock proteins -- HspBP1 (Hsp70) binding protein 1 -- MHC Major histocompatibility complex -- ATP Adenosine triphosphate -- ADP Adenosine diphosphate -- GRP78 Glucose regulated protein 78 -- PBD Peptide binding domain -- ABD ATP binding domain -- PS Phosphatidylserine -- PKB Protein kinase B -- BH Bcl2 homology -- Bak Bcl2 homologous antagonist/killer -- Bax Bcl2 associated X protein -- Bcl-Xs B cell lymphoma X small -- BclxL B cell lymphoma x Large -- Bcl2 B cell lymphoma 2 -- Bid BH3 interacting-domain death agonist -- CAD Caspase-activated DNase -- Caspase Cysteinyl aspartate protease -- ING Inhibitor of growth -- IKK Inhibition of I-kB-α kinase -- ER Endoplasmic reticulum -- MPT Membrane permeability transition -- BH3-OFM BH3-only family member -- OMM Outer mitochondrial membrane -- PTP Permeability transition pores -- TM Transmembrane domains -- CYT-C Cytochrome-c -- CARD Caspase activation and recruitment domain -- Apaf-1 Apoptotic protease activating factor-1 -- ICE Interleukin-1β converting enzyme -- DED Death effector domain -- FADD Fas-associating death domain -- DISC Death inducing signaling complex -- TRAIL TNF-related apoptosis inducing ligand -- TRAIL-R TNF-related apoptosis inducing ligand-receptor -- Smac Second mitochondrial activator of caspase -- DIBALO Direct IAP binding protein with low pI -- Endo-G Endonuclease G -- DR Death receptor -- NGF Nerve growth factor -- NGFR Nerve growth factor receptor -- siRNA Short interfering RNA -- RNAi RNA interference -- TNF-α Tumor necrosis factor alpha -- ASK-1 Stress activated kinase-1 -- FasL Fas-ligand -- DD Death domain -- NF-kB Nuclear factor-kappa-B -- t-Bid Truncated-Bid -- XIAP X-linked IAP -- HSFs Heat shock factors -- HSF1 Heat shock factor1 -- DBD DNA binding domain -- AIF Apoptosis inducing factor -- SAPK Stress activated kinase -- JNK c-Jun N-terminal kinase -- DAG Diacylglycerol -- PARP Poly (ADP-ribose) polymerase -- ADD70 AIF-derived decoy for Hsp70 -- APCs Antigen presenting cells -- CD Cluster of differentiation -- NK cells Natural killer cells; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.01.056
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Hsp70 promotes tumor cell survival by interacting at several points in apoptotic signaling pathway(s). Interaction on different immunological and immunotherapeutic impacts of Hsp70 in cancer cell survival are summarized. Advance strategies to target Hsp70 are discussed and future directions are proposed. Hsp70 can be used as an immunotherapeutic drug because its potent adjuvant nature induces cancer autoimmunity. 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.