Heat Shock Protein 70 and Cancer

  • Tuoen LiuEmail author
  • Shousong Cao
Part of the Heat Shock Proteins book series (HESP, volume 14)


Heat shock proteins (HSP) constitute a large family of proteins involved in protein folding and maturation and the expressions of HSP are induced by heat shock or other stressors. The major groups, which are classified based on their molecular weight, include HSP27, HSP40, HSP60, HSP70, HSP90, and large HSP (HSP110 and glucose-regulated protein 170). The human HSP70 family is consists of 13 members and five of them have a strong association with cancer. HSP play a significant role in cellular proliferation, differentiation, survival, apoptosis, and carcinogenesis. In this chapter, we thoroughly discussed the roles of HSP70s in cancer biology and pharmacology. The HSP70 proteins have important functions in the molecular mechanisms leading to cancer development, progression, and metastasis. They may also have potential clinical use as biomarkers for cancer diagnosis or assessing disease progression, and as therapeutic targets for cancer therapy. Understanding of the functions and molecular mechanisms of HSP70 proteins is critical for enhancing the accuracy of cancer diagnosis as well as for developing more effective and less toxic chemotherapeutic agents.


Biomarker Cancer Carcinogenesis Heat shock protein 70 Therapeutic target 





adenosine diphosphate


apoptosis-inducing factor


protein kinase B


acute lymphoid leukemia


acute myelogenous leukemia


AMP-activated protein kinase


apoptotic protease activating factor 1


activating transcription factor


adenosine triphosphate


adenosine triphosphatase


Bcl-2 associated athanogene 1


Bcl-2 associated X


B-cell lymphoma-2


B-cell lymphoma-extra-large


Bcl-2 interacting killer


binding immunoglobulin protein


v-raf murine sarcoma viral oncogene homolog B


cyclin-dependent kinase


carboxyl-terminus of HSP70-interacting protein


chronic myeloid leukemia


v-raf murine sarcoma viral oncogene homolog C




epidermal growth factor receptor


epithelial-mesenchymal transition


endoplasmic reticulum


Ras/extracellular signal-regulated kinase


Food and Drug Administration


glucose-regulated protein


hepatitis B virus


histone deacetylases


human epidermal growth factor receptor 2


human immunodeficiency virus


heat-shock cognate protein


heat shock element


heat shock factor


heat shock protein


Human Genome Organization




Janus kinase


mitogen-activated protein kinase


myeloid cell leukemia 1


mitogen-activated protein kinase kinase


mechanistic target of rapamycin




nuclear factor NF-κB


non-small cell lung cancer;


oxidative modified low density lipoprotein






phosphatidylinositol-4, 5-bisphosphate 3-kinase


prostate-specific antigen


suberanilohydroxamic acid


sphingosine kinase 1


signal transducer and activator of transcription


transforming growth factor


tumor necrosis factor;


TNF-α-induced protein 3-interacting protein 1


UBX Domain Protein 2A



This work was supported by the West Virginia School of Osteopathic Medicine faculty startup funding (T. Liu); and the Distinguished Professor Research Startup Funding (S. Cao) from Southwest Medical University, Lanzhou, Sichuan, China.


  1. Akerfelt, M., Morimoto, R. I., & Sistonen, L. (2010). Heat shock factors: Integrators of cell stress, development and lifespan. Nature Reviews. Molecular Cell Biology, 11(8), 545–533.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Ando, K., Oki, Z., Zhao, Y., et al. (2014). Mortalin is a prognostic factor of gastric cancer with normal p53 function. Gastric Cancer, 17(2), 255–262.CrossRefPubMedGoogle Scholar
  3. Arafa, e.-S. A., Abdelazeem, A. H., Arab, H. H., et al. (2014). OSU-CG5, a novel energy restriction mimetic agent, targets human colorectal cancer cells in vitro. Acta Pharmacologica Sinica, 35(3), 394–400.CrossRefPubMedCentralGoogle Scholar
  4. Arispe, N., & De Maio, A. (2000). ATP and ADP modulate a cation channel formed by Hsc70 in acidic phospholipid membranes. The Journal of Biological Chemistry, 275(40), 30839–30843.CrossRefPubMedGoogle Scholar
  5. Bakkenist, C. J., Koreth, J., Williams, C. S., et al. (1999). Heat shock cognate 70 mutations in sporadic breast carcinoma. Cancer Research, 59(17), 4219–4221.PubMedGoogle Scholar
  6. Balaburski, G. M., Leu, J. J., Beeharry, N., et al. (2013). A modified HSP70 inhibitor shows broad activity as an anticancer agent. Molecular Cancer Research, 11(3), 219–229.CrossRefPubMedGoogle Scholar
  7. Bayer, C., Liebhardt, M. E., Schmid, T. E., et al. (2014). Validation of heat shock protein 70 as a tumor-specific biomarker for monitoring the outcome of radiation therapy in tumor mouse models. International Journal of Radiation Oncology, Biology, Physics, 88(3), 694–700.CrossRefPubMedGoogle Scholar
  8. Bepperling, A., Alte, F., Kriehuber, T., et al. (2012). Alternative bacterial two-component small heat shock protein systems. Proceedings of the National Academy of Sciences of the United States of America, 109(50), 20407–20412.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Boonjaraspinyo, S., Boonmars, T., Kaewkes, S., et al. (2012). Down-regulated expression of HSP70 in correlation with clinicopathology of cholangiocarcinoma. Pathology Oncology Research, 18(2), 227–237.CrossRefPubMedGoogle Scholar
  10. Cai, M. B., Wang, X. P., Zhang, J. X., et al. (2012). Expression of heat shock protein 70 in nasopharyngeal carcinomas: Different expression patterns correlate with distinct clinical prognosis. Journal of Translational Medicine, 10, 96.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Chakravarty, G., Mathur, A., Mallade, P., et al. (2016). Nelfinavir targets multiple drug resistance mechanisms to increase the efficacy of doxorubicin in MCF-7/Dox breast cancer cells. Biochimie, 124, 53–64.CrossRefPubMedGoogle Scholar
  12. Chen, T. H., Kambal, A., Krysiak, K., et al. (2011). Knockdown of Hspa9, a del(5q31.2) gene, results in a decrease in hematopoietic progenitors in mice. Blood, 117(5), 1530–1539.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Chen, J., Liu, W. B., Jia, W. D., et al. (2014). Overexpression of Mortalin in hepatocellular carcinoma and its relationship with angiogenesis and epithelial to mesenchymal transition. International Journal of Oncology, 44(1), 247–255.CrossRefPubMedGoogle Scholar
  14. Chiou, J. F., Tai, C. J., Huang, M. T., et al. (2010). Glucose-regulated protein 78 is a novel contributor to acquisition of resistance to sorafenib in hepatocellular carcinoma. Annals of Surgical Oncology, 17(2), 603–612.CrossRefPubMedGoogle Scholar
  15. Ciocca, D. R., & Calderwood, S. K. (2005). Heat shock proteins in cancer: Diagnostic, prognostic, predictive, and treatment implications. Cell Stress & Chaperones, 10(2), 86–103.CrossRefGoogle Scholar
  16. Fu, Y., Li, J., & Lee, A. S. (2007). GRP78/BiP inhibits endoplasmic reticulum BIK and protects human breast cancer cells against estrogen starvation-induced apoptosis. Cancer Research, 67(8), 3734–3740.CrossRefPubMedGoogle Scholar
  17. Gabai, V. L., Yaglom, J. A., Waldman, T., & Sherman, M. Y. (2009). Heat shock protein Hsp72 controls oncogene-induced senescence pathways in cancer cells. Molecular and Cellular Biology, 29(2), 559–569.CrossRefPubMedGoogle Scholar
  18. Gestl, E. E., & Anne Böttger, S. (2012). Cytoplasmic sequestration of the tumor suppressor p53 by a heat shock protein 70 family member, mortalin, in human colorectal adenocarcinoma cell lines. Biochemical and Biophysical Research Communications, 423(2), 411–416.CrossRefPubMedGoogle Scholar
  19. Gray, P. C., & Vale, W. (2012). Cripto/GRP78 modulation of the TGF-β pathway in development and oncogenesis. FEBS Letters, 586(4), 1836–1845.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Hanke, N. T., Garland, L. L., & Baker, A. F. (2016). Carfilzomib combined with suberanilohydroxamic acid (SAHA) synergistically promotes endoplasmic reticulum stress in non-small cell lung cancer cell lines. Journal of Cancer Research and Clinical Oncology, 142(3), 549–560.CrossRefPubMedGoogle Scholar
  21. Helmbrecht, K., & Rensing, L. (1999). Different constitutive heat shock protein 70 expression during proliferation and differentiation of rat C6 glioma cells. Neurochemical Research, 24(10), 1293–1299.CrossRefPubMedGoogle Scholar
  22. Howe, M. K., Bodoor, K., Carlson, D. A., et al. (2014). Identification of an allosteric small-molecule inhibitor selective for the inducible form of heat shock protein 70. Chemistry & Biology, 21(12), 1648–1659.CrossRefGoogle Scholar
  23. Hu, Y., Yang, L., Yang, Y., et al. (2016). Oncogenic role of mortalin contributes to ovarian tumorigenesis by activating the MAPK-ERK pathway. Journal of Cellular and Molecular Medicine, 20(11), 2111–2121.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Hung, C. M., Su, Y. H., Lin, J. N., et al. (2012). Demethoxycurcumin modulates prostate cancer cell proliferation via AMPK-induced down-regulation of HSP70 and EGFR. Journal of Agricultural and Food Chemistry, 60(34), 8427–8434.CrossRefPubMedGoogle Scholar
  25. Jäättelä, M., Wissing, D., Bauer, P. A., et al. (1992). Major heat shock protein hsp70 protects tumor cells from tumor necrosis factor cytotoxicity. The EMBO Journal, 11(10), 3507–3512.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Jakob, U., Scheibel, T., Bose, S., Reinstein, J., et al. (1996). Assessment of the ATP binding properties of Hsp90. The Journal of Biological Chemistry, 271(17), 10035–10041.CrossRefPubMedGoogle Scholar
  27. Jiang, C. C., Mao, Z. G., Avery-Kiejda, K. A., et al. (2009). Glucose-regulated protein 78 antagonizes cisplatin and adriamycin in human melanoma cells. Carcinogenesis, 30(2), 197–204.CrossRefPubMedGoogle Scholar
  28. Jin, H., Ji, M., Chen, L., et al. (2016). The clinicopathological significance of Mortalin overexpression in invasive ductal carcinoma of breast. Journal of Experimental & Clinical Cancer Research, 35, 42.CrossRefGoogle Scholar
  29. Jung, J. H., Lee, J. O., Kim, J. H., et al. (2010). Quercetin suppresses HeLa cell viability via AMPK-induced HSP70 and EGFR down-regulation. Journal of Cellular Physiology, 223(2), 408–414.PubMedGoogle Scholar
  30. Kaiser, M., Lee, J. O., Kim, J. H., et al. (2011). Antileukemic activity of the HSP70 inhibitor pifithrin-μ in acute leukemia. Blood Cancer Journal, 1(7), e28.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Kampinga, H. H., Hageman, J., Vos, M. J., et al. (2009). Guidelines for the nomenclature of the human heat shock proteins. Cell Stress & Chaperones, 14(1), 105–111.CrossRefGoogle Scholar
  32. Khalouei, S., Chow, A. M., Brown, I. R. (2014). Localization of heat shock protein HSPA6 (HSP70B′) to sites of transcription in cultured differentiated human neuronal cells following thermal stress. Journal of Neurochemistry, 131(6), 743–754.CrossRefPubMedGoogle Scholar
  33. Kim, J. A., Kim, Y., Kwon, B. M., et al. (2013). The natural compound cantharidin induces cancer cell death through inhibition of heat shock protein 70 (HSP70) and Bcl-2-associated athanogene domain 3 (BAG3) expression by blocking heat shock factor 1 (HSF1) binding to promoters. The Journal of Biological Chemistry, 288(40), 28713–28726.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Kim, J. A., Lee, S., Kim, D. E., et al. (2015). Fisetin, a dietary flavonoid, induces apoptosis of cancer cells by inhibiting HSF1 activity through blocking its binding to the hsp70 promoter. Carcinogenesis, 36(6), 696–706.CrossRefPubMedGoogle Scholar
  35. Ko, S. K., Kim, J., Na, D. C., et al. (2015). A small molecule inhibitor of ATPase activity of HSP70 induces apoptosis and has antitumor activities. Chemistry & Biology, 22(3), 391–403.CrossRefGoogle Scholar
  36. Kocsis, J., Mészáros, T., Madaras, B., et al. (2011). High levels of acute phase proteins and soluble 70 kDa heat shock proteins are independent and additive risk factors for mortality in colorectal cancer. Cell Stress & Chaperones, 16(1), 49–55.CrossRefGoogle Scholar
  37. Kosakowska-Cholody, T., Lin, J., Srideshikan, S. M., et al. (2014). HKH40A downregulates GRP78/BiP expression in cancer cells. Cell Death & Disease, 5, e1240.CrossRefGoogle Scholar
  38. Kuballa, P., Baumann, A. L., Mayer, K., et al. (2015). Induction of heat shock protein HSPA6 (HSP70B′) upon HSP90 inhibition in cancer cell lines. FEBS Letters, 589(13):1450–1458.CrossRefPubMedGoogle Scholar
  39. Kubota, H., Yamamoto, S., Itoh, E., et al. (2010). Increased expression of co-chaperone HOP with HSP90 and HSC70 and complex formation in human colonic carcinoma. Cell Stress & Chaperones, 15(6), 1003–1011.CrossRefGoogle Scholar
  40. Lee, A. S. (2007). GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Research, 67(8), 3496–3499.CrossRefPubMedGoogle Scholar
  41. Leung, T. K., Rajendran, M. Y., Monfries, C., et al. (1990). The human heat-shock protein family. Expression of a novel heat-inducible HSP70 (HSP70B′) and isolation of its cDNA and genomic DNA. The Biochemical Journal, 267: 125–132.CrossRefPubMedPubMedCentralGoogle Scholar
  42. Li, J., Ni, M., Lee, B., et al. (2008). The unfolded protein response regulator GRP78/BiP is required for endoplasmic reticulum integrity and stress-induced autophagy in mammalian cells. Cell Death & Disease, 15(9), 1460–1471.CrossRefGoogle Scholar
  43. Li, G., Xu, Y., Guan, D., et al. (2011). HSP70 protein promotes survival of C6 and U87 glioma cells by inhibition of ATF5 degradation. The Journal of Biological Chemistry, 286(23), 20251–20259.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Li, X., Srinivasan, S. R., Connarn, J., et al. (2013). Analogs of the allosteric heat shock protein 70 (Hsp70) inhibitor, MKT-077, as anti-cancer agents. ACS Medicinal Chemistry Letters, 4(11), 1042–1047.CrossRefPubMedCentralGoogle Scholar
  45. Lin, Y., Wang, Z., Liu, L., & Chen, L. (2011). Akt is the downstream target of GRP78 in mediating cisplatin resistance in ER stress-tolerant human lung cancer cells. Lung Cancer, 71(3), 291–297.CrossRefPubMedGoogle Scholar
  46. Liu, T., Daniels, C. K., & Cao, S. (2012). Comprehensive review on the HSC70 functions, interactions with related molecules and involvement in clinical diseases and therapeutic potential. Pharmacology & Therapeutics, 136(3), 354–374.CrossRefGoogle Scholar
  47. Liu, T., Singh, R., Rios, Z., et al. (2015). Tyrosine phosphorylation of HSC70 and its interaction with RFC mediates methotrexate resistance in murine L1210 leukemia cells. Cancer Letters, 357(1), 231–241.CrossRefPubMedGoogle Scholar
  48. Liu, T., Krysiak, K., Shirai, C. L., et al. (2017). Knockdown of HSPA9 induces TP53-dependent apoptosis in human hematopoietic progenitor cells. PLoS One, 12(2), e0170470.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Lu, W. J., Lee, N. P., Kaul, S. C., et al. (2011). Induction of mutant p53-dependent apoptosis in human hepatocellular carcinoma by targeting stress protein mortalin. International Journal of Cancer, 129(8), 1806–1814.CrossRefPubMedGoogle Scholar
  50. Ma, Y., & Hendershot, L. M. (2004). The role of the unfolded protein response in tumor development: Friend or foe? Nature Reviews. Cancer, 4(12), 966–967.CrossRefPubMedGoogle Scholar
  51. Ma, X. H., Piao, S. F., Dey, S., et al. (2014). Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. The Journal of Clinical Investigation, 124(3), 1406–1417.CrossRefPubMedPubMedCentralGoogle Scholar
  52. Macario, A. J., & Conway de Macario, E. (2007). Molecular chaperones: multiple functions, pathologies, and potential applications. Frontiers in Bioscience, 1(12), 2588–2600.CrossRefGoogle Scholar
  53. Misra, U. K., Mowery, Y., Kaczowka, S., et al. (2009). Ligation of cancer cell surface GRP78 with antibodies directed against its COOH-terminal domain up-regulates p53 activity and promotes apoptosis. Molecular Cancer Therapeutics, 8(5), 1350–1362.CrossRefPubMedGoogle Scholar
  54. Misra, U. K., Payne, S., & Pizzo, S. (2011). Ligation of prostate cancer cell surface GRP78 activates a proproliferative and antiapoptotic feedback loop: A role for secreted prostate-specific antigen. The Journal of Biological Chemistry, 286(2), 1248–1259.CrossRefPubMedGoogle Scholar
  55. Moghanibashi, M., Rastgar-Jazii, F., Soheili, Z. S., et al. (2013). Esophageal cancer alters the expression of nuclear pore complex binding protein Hsc70 and eIF5A-1. Functional & Integrative Genomics, 13(2), 253–260.CrossRefGoogle Scholar
  56. Moon, J. Y., & Cho, S. K. (2016). Nobiletin induces protective autophagy accompanied by ER-stress mediated apoptosis in human gastric cancer SNU-16 cells. Molecules, 21(7), 914.CrossRefGoogle Scholar
  57. Murphy, M. E. (2013). The HSP70 family and cancer. Carcinogenesis, 34(6), 1181–1188.CrossRefPubMedPubMedCentralGoogle Scholar
  58. Na, Y., Kaul, S. C., Ryu, J., et al. (2016). Stress chaperone mortalin contributes to epithelial-mesenchymal transition and cancer metastasis. Cancer Research, 76(9), 2764–2765.CrossRefGoogle Scholar
  59. Nigam, N., Grover, A., Goyal, S., et al. (2015). Targeting mortalin by embelin causes activation of tumor suppressor p53 and deactivation of metastatic signaling in human breast cancer cells. PLoS One, 10(9), e0138192.CrossRefPubMedPubMedCentralGoogle Scholar
  60. Noonan, E. J., Fournier, G., Hightower, L. E. (2008). Surface expression of Hsp70B′ in response to proteasome inhibition in human colon cells. Cell Stress & Chaperones, 13(1), 105–110.CrossRefPubMedGoogle Scholar
  61. Nylandsted, J., Gyrd-Hansen, M., Danielewicz, A., et al. (2004). Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. The Journal of Experimental Medicine, 200(4), 425–435.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Pilzer, D., Saar, M., Koya, K., et al. (2010). Mortalin inhibitors sensitize K562 leukemia cells to complement-dependent cytotoxicity. International Journal of Cancer, 126(6), 1428–1435.PubMedGoogle Scholar
  63. Qi, W., White, M. C., Choi, W., et al. (2013). Inhibition of inducible heat shock protein-70 (hsp72) enhances bortezomib-induced cell death in human bladder cancer cells. PLoS One, 8(7), e69509.CrossRefPubMedPubMedCentralGoogle Scholar
  64. Ramired, V. P., Krueger, W., & Aneskievich, B. J. (2015). TNIP1 reduction of HSPA6 gene expression occurs in promoter regions lacking binding sites for known TNIP1-repressed transcription factors. Gene, 555(2), 430–437.CrossRefGoogle Scholar
  65. Ramp, U., Mahotka, C., Heikaus, S., et al. (2007). Expression of heat shock protein 70 in renal cell carcinoma and its relation to tumor progression and prognosis. Histology and Histopathology, 22(10), 1099–1107.PubMedGoogle Scholar
  66. Reddy, R. K., Mao, C., Baumeister, P., et al. (2003). Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: Role of ATP binding site in suppression of caspase-7 activation. The Journal of Biological Chemistry, 278(23), 20915–20924.CrossRefPubMedGoogle Scholar
  67. Regeling, A., Imhann, F., Volders, H. H., et al. (2016). HSPA6 is an ulcerative colitis susceptibility factor that is induced by cigarette smoke and protects intestinal epithelial cells by stabilizing anti-apoptotic Bcl-XL. Biochimica et Biophysica Acta, 1862, 788–796.CrossRefPubMedGoogle Scholar
  68. Rérole, A. L., Jego, G., & Garrido, C. (2011). Hsp70: Anti-apoptotic and tumorigenic protein. Methods in Molecular Biology, 787, 205–230.CrossRefPubMedGoogle Scholar
  69. Roberts, J. L., Tavallai, M., Nourbakhsh, A., et al. (2015). GRP78/Dna K is a target for nexavar/stivarga/votrient in the treatment of human malignancies, viral infections and bacterial diseases. Journal of Cellular Physiology, 230(10), 2552–2578.CrossRefPubMedPubMedCentralGoogle Scholar
  70. Roller, C., & Maddalo, D. (2013). The Molecular chaperone GRP78/BiP in the development of chemoresistance: Mechanism and possible treatment. Frontiers in Pharmacology, 4, 10.CrossRefPubMedPubMedCentralGoogle Scholar
  71. Rozenberg, P., Kocsis, J., Saar, M., et al. (2013). Elevated levels of mitochondrial mortalin and cytosolic HSP70 in blood as risk factors in patients with colorectal cancer. International Journal of Cancer, 133(2), 514–518.CrossRefPubMedGoogle Scholar
  72. Rusin, M., Zientek, H., Krześniak, M., et al. (2004). Intronic polymorphism (1541-1542delGT) of the constitutive heat shock protein 70 gene has functional significance and shows evidence of association with lung cancer risk. Molecular Carcinogenesis, 39(3), 155–163.CrossRefPubMedGoogle Scholar
  73. Sandoval, J. A., Hoelz, D. J., Woodruff, H. A., et al. (2006). Novel peptides secreted from human neuroblastoma: Useful clinical tools? Journal of Pediatric Surgery, 41(1), 245–251.CrossRefPubMedGoogle Scholar
  74. Sane, S., Abdullah, A., Nelson, M. E., et al. (2016). Structural studies of UBXN2A and mortalin interaction and the putative role of silenced UBXN2A in preventing response to chemotherapy. Cell Stress & Chaperones, 21(2), 313–326.CrossRefGoogle Scholar
  75. Sekihara, K., Harashima, N., Tongu, M., et al. (2013). Pifithrin-μ, an inhibitor of heat-shock protein 70, can increase the antitumor effects of hyperthermia against human prostate cancer cells. PLoS One, 8(11), e78772.CrossRefPubMedPubMedCentralGoogle Scholar
  76. Smith, K. J. (2010). Heat shock protein 70B′ (HSP70B′) expression and release in response to human oxidized low density lipoprotein immune complexes in macrophages. The Journal of Biological Chemistry, 285(21), 15985–15993.CrossRefPubMedGoogle Scholar
  77. Sobolewski, C., Rhim, J., Legrand, N., et al. (2015). 2,5-Dimethyl-celecoxib inhibits cell cycle progression and induces apoptosis in human leukemia cells. The Journal of Pharmacology and Experimental Therapeutics, 355(2), 308–328.CrossRefPubMedGoogle Scholar
  78. Song, L., Liu, H., Ma, L., et al. (2013). Inhibition of autophagy by 3-MA enhances endoplasmic reticulum stress-induced apoptosis in human nasopharyngeal carcinoma cells. Oncology Letters, 6(4), 1031–1038.CrossRefPubMedPubMedCentralGoogle Scholar
  79. Starenki, D., Hong, S. K., Lloyd, R. V., et al. (2015). Mortalin (GRP75/HSPA9) upregulation promotes survival and proliferation of medullary thyroid carcinoma cells. Oncogene, 34(35), 4624–4634.CrossRefPubMedGoogle Scholar
  80. Sugita, S., Ito, K., Yamashiro, Y., et al. (2015). EGFR-independent autophagy induction with gefitinib and enhancement of its cytotoxic effect by targeting autophagy with clarithromycin in non-small cell lung cancer cells. Biochemical and Biophysical Research Communications, 461(1), 28–34.CrossRefPubMedGoogle Scholar
  81. Sullivan, C. S., & Pipas, J. M. (2002). T antigens of simian virus 40: Molecular chaperones for viral replication and tumorigenesis. Microbiology and Molecular Biology Reviews, 66(2), 179–202.CrossRefPubMedPubMedCentralGoogle Scholar
  82. Takahashi, K., Tanaka, M., Yashiro, M., et al. (2016). Protection of stromal cell-derived factor 2 by heat shock protein 72 prevents oxaliplatin-induced cell death in oxaliplatin-resistant human gastric cancer cells. Cancer Letters, 378(1), 8–15.CrossRefPubMedGoogle Scholar
  83. Tanaka, M., Mun, S., Harada, A., et al. (2014). Hsc70 contributes to cancer cell survival by preventing Rab1A degradation under stress conditions. PLoS One, 9(5), e96785.CrossRefPubMedPubMedCentralGoogle Scholar
  84. Tavallai, M., Booth, L., Roberts, J. L., et al. (2016). Rationally repurposing Ruxolitinib (Jakafi (®)) as a solid tumor therapeutic. Frontiers in Oncology, 6, 142.CrossRefPubMedPubMedCentralGoogle Scholar
  85. Trieb, K., Sulzbacher, I., & Kubista, B. (2016). Recurrence rate and progression of chondrosarcoma is correlated with heat shock protein expression. Oncology Letters, 11(1), 521–524.CrossRefPubMedGoogle Scholar
  86. Ulianich, L., & Insabato, L. (2014). Endoplasmic reticulum stress in endometrial cancer. Frontiers of Medical (Lausanne), 1, 55.Google Scholar
  87. Wadhwa, R., Sugihara, T., Yoshida, A., et al. (2000). Selective toxicity of MKT-077 to cancer cells is mediated by its binding to the hsp70 family protein mot-2 and reactivation of p53 function. Cancer Research, 60(24), 6818–6821.PubMedGoogle Scholar
  88. Wang, X., Wang, Q., & Lin, H. (2010). Correlation between clinicopathology and expression of heat shock protein 72 and glycoprotein 96 in human esophageal squamous cell carcinoma. Clinical & Developmental Immunology, 2010, 212537.Google Scholar
  89. Wang, N., Wang, Z., Peng, C., et al. (2014a). Dietary compound isoliquiritigenin targets GRP78 to chemosensitize breast cancer stem cells via β-catenin/ABCG2 signaling. Carcinogenesis, 35(11), 2544–2554.CrossRefPubMedGoogle Scholar
  90. Wang, X., Chen, M., Zhou, J., et al. (2014b). HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy (Review). International Journal of Oncology, 45(1), 18–30.CrossRefPubMedGoogle Scholar
  91. Wu, J., Liu, T., Rios, Z., et al. (2017). Heat shock proteins and cancer. Trends in Pharmacological Sciences, 38(3), 226–256.CrossRefPubMedGoogle Scholar
  92. Yang, L., Li, H., Jiang, Y., et al. (2013). Inhibition of mortalin expression reverses cisplatin resistance and attenuates growth of ovarian cancer cells. Cancer Letters, 336(1), 213–221.CrossRefPubMedGoogle Scholar
  93. Yang, Z., Zhuang, L., Szatmary, P., et al. (2015). Upregulation of heat shock proteins (HSPA12A, HSP90B1, HSPA4, HSPA5 and HSPA6) in tumour tissues is associated with poor outcomes from HBV-related early-stage hepatocellular carcinoma. International Journal of Medical Sciences, 12(3), 256–263.CrossRefPubMedPubMedCentralGoogle Scholar
  94. Yerushalmi, R., Raiter, A., Nalbandvan, K., & Hardy, B. (2015). Cell surface GRP78: A potential marker of good prognosis and response to chemotherapy in breast cancer. Oncology Letters, 10(4), 2149–2155.CrossRefPubMedPubMedCentralGoogle Scholar
  95. Yi, X., Luk, J. M., Lee, N. P., et al. (2008). Association of mortalin (HSPA9) with liver cancer metastasis and prediction for early tumor recurrence. Molecular & Cellular Proteomics, 7(2), 315–325.CrossRefGoogle Scholar
  96. Yoshidomi, K., Murakami, A., Yakabe, K., et al. (2014). Heat shock protein 70 is involved in malignant behaviors and chemosensitivities to cisplatin in cervical squamous cell carcinoma cells. The Journal of Obstetrics and Gynaecology Research, 40(5), 1188–1196.CrossRefPubMedGoogle Scholar
  97. Yuan, L., Zhang, L., Dong, X., et al. (2013). Apoptin selectively induces the apoptosis of tumor cells by suppressing the transcription of HSP70. Tumour Biology, 34(1), 577–585.CrossRefPubMedGoogle Scholar
  98. Zhang, H., Hu, H., Jiang, X., et al. (2005). Membrane HSP70: The molecule triggering gammadelta T cells in the early stage of tumorigenesis. Immunological Investigations, 34(4), 453–468.CrossRefPubMedGoogle Scholar
  99. Zhao, L., Li, H., Shi, Y., et al. (2014). Nanoparticles inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery via cell surface-related GRP78. International Journal of Nanomedicine, 10, 245–256.CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biomedical SciencesWest Virginia School of Osteopathic MedicineLewisburgUSA
  2. 2.Department of Pharmacology, School of PharmacySouthwest Medical UniversityLuzhouChina

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