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HSPA6 and its role in cancers and other diseases

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Abstract

Heat Shock Protein Family A (Hsp70) Member 6 (HSPA6) (Online Mendelian Inheritance in Man: 140555) belongs to the HSP70 family and is a partially conserved inducible protein in mammals. The HSPA6 gene locates on the human chromosome 1q23.3 and encodes a protein containing two important structural domains: The N-terminal nucleotide-binding domain and the C-terminal substrate-binding domain. Currently, studies have found that HSPA6 not only plays a role in the tumorigenesis and tumor progresses but also causes non-tumor-related diseases. Furthermore, HSPA6 exhibits to inhibit tumorigenesis and tumor progression in some types of cancers but promotes in others. Even though HSPA6 research has increased, its exact roles and mechanisms are still unclear. This article reviews the structure, expression, function, research progress, possible mechanism, and perspective of HSPA6 in cancers and other diseases, highlighting its potential role as a targeted therapeutic and prognostic marker.

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References

  1. Leung TK, Rajendran MY, 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. Biochem J 267(1):125–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Vos MJ, Hageman J, Carra S et al (2008) Structural and functional diversities between members of the human HSPB, HSPH, HSPA, and DNAJ chaperone families. Biochemistry 47:7001–7011

    Article  CAS  PubMed  Google Scholar 

  3. Radons J (2016) The human HSP70 family of chaperones: where do we stand? Cell Stress Chaperones 21:379–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Vostakolaei MA, Hatami-Baroogh L, Babaei G et al (2021) Hsp70 in cancer: a double agent in the battle between survival and death. J Cell Physiol 236:3420–3444

    Article  CAS  PubMed  Google Scholar 

  5. Ambrose AJ, Chapman E (2021) Function, therapeutic potential, and inhibition of Hsp70 chaperones. J Med Chem 64:7060–7082

    Article  CAS  PubMed  Google Scholar 

  6. Amberger JS, Hamosh A (2017) Searching online mendelian inheritance in man (OMIM): a knowledgebase of human genes and genetic phenotypes. Curr Protoc Bioinform. https://doi.org/10.1002/cpbi.27

    Article  Google Scholar 

  7. Flaherty KM, DeLuca-Flaherty C, McKay DB (1990) Three-dimensional structure of the ATPase fragment of a 70 K heat-shock cognate protein. Nature 346:623–628

    Article  CAS  PubMed  Google Scholar 

  8. English CA, Sherman W, Meng W et al (2017) The Hsp70 interdomain linker is a dynamic switch that enables allosteric communication between two structured domains. J Biol Chem 292:14765–14774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wisniewska M, Karlberg T, Lehtio L et al (2010) Crystal structures of the ATPase domains of four human Hsp70 isoforms: HSPA1L/Hsp70-hom, HSPA2/Hsp70-2, HSPA6/Hsp70B’, and HSPA5/BiP/GRP78. PLoS ONE 5:e8625

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zhu X, Zhao X, Burkholder WF et al (1996) Structural analysis of substrate binding by the molecular chaperone DnaK. Science 272:1606–1614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kohler V, Andreasson C (2020) Hsp70-mediated quality control: should I stay or should I go? Biol Chem 401:1233–1248

    Article  CAS  PubMed  Google Scholar 

  12. Havalova H, Ondrovicova G, Keresztesova B et al (2021) Mitochondrial HSP70 chaperone system-the influence of post-translational modifications and involvement in human diseases. Int J Mol Sci 22(15):8077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Rosenzweig R, Nillegoda NB, Mayer MP et al (2019) The Hsp70 chaperone network. Nat Rev Mol Cell Biol 20:665–680

    Article  CAS  PubMed  Google Scholar 

  14. Zhuravleva A, Clerico EM, Gierasch LM (2012) An interdomain energetic tug-of-war creates the allosterically active state in Hsp70 molecular chaperones. Cell 151:1296–1307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hageman J, van Waarde MA, Zylicz A et al (2011) The diverse members of the mammalian HSP70 machine show distinct chaperone-like activities. Biochem J 435:127–142

    Article  CAS  PubMed  Google Scholar 

  16. Hartl FU (1996) Molecular chaperones in cellular protein folding. Nature 381:571–579

    Article  CAS  PubMed  Google Scholar 

  17. Sharma SK, De los Rios P, Christen P et al (2010) The kinetic parameters and energy cost of the Hsp70 chaperone as a polypeptide unfoldase. Nat Chem Biol 6:914–920

    Article  CAS  PubMed  Google Scholar 

  18. Finka A, Sharma SK, Goloubinoff P (2015) Multi-layered molecular mechanisms of polypeptide holding, unfolding and disaggregation by HSP70/HSP110 chaperones. Front Mol Biosci 2:29

    Article  PubMed  PubMed Central  Google Scholar 

  19. Truman AW, Bourboulia D, Mollapour M (2021) Decrypting the chaperone code. J Biol Chem 296:100293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nitika PCM, Truman AW et al (2020) Post-translational modifications of Hsp70 family proteins: expanding the chaperone code. J Biol Chem 295(31):10689–10708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jakobsson ME, Moen A, Bousset L et al (2013) Identification and characterization of a novel human methyltransferase modulating Hsp70 protein function through lysine methylation. J Biol Chem 288:27752–27763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cheng J, Zhou J, Fu S et al (2021) Prostate adenocarcinoma and COVID-19: the possible impacts of TMPRSS2 expressions in susceptibility to SARS-CoV-2. J Cell Mol Med 25:4157–4165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schumpert C, Handy I, Dudycha JL et al (2014) Relationship between heat shock protein 70 expression and life span in Daphnia. Mech Ageing Dev 139:1–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. de Toda IM, Vida C, Ortega E et al (2016) Hsp70 basal levels, a tissue marker of the rate of aging and longevity in mice. Exp Gerontol 84:21–28

    Article  PubMed  Google Scholar 

  25. Shilova V, Zatsepina O, Zakluta A et al (2020) Age-dependent expression profiles of two adaptogenic systems and thermotolerance in Drosophila melanogaster. Cell Stress Chaperones 25:305–315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Uhlen M, Fagerberg L, Hallstrom BM et al (2015) Tissue-based map of the human proteome. Science 347:1260419

    Article  PubMed  Google Scholar 

  27. Fu J, Wei C, He J et al (2021) Evaluation and characterization of HSPA5 (GRP78) expression profiles in normal individuals and cancer patients with COVID-19. Int J Biol Sci 17:897–910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Tang Z, Kang B, Li C et al (2019) GEPIA2: an enhanced web server for large-scale expression profiling and interactive analysis. Nucleic Acids Res 47:W556–W560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Shin SS, Song JH, Hwang B et al (2017) HSPA6 augments garlic extract-induced inhibition of proliferation, migration, and invasion of bladder cancer EJ cells; implication for cell cycle dysregulation, signaling pathway alteration, and transcription factor-associated MMP-9 regulation. PLoS ONE 12:e0171860

    Article  PubMed  PubMed Central  Google Scholar 

  30. Duncan RM, Reyes L, Moats K et al (2020) ATF3 coordinates antitumor synergy between epigenetic drugs and protein disulfide isomerase inhibitors. Cancer Res 80:3279–3291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hua AB, Justiniano R, Perer J et al (2019) Repurposing the electron transfer reactant phenazine methosulfate (PMS) for the apoptotic elimination of malignant melanoma cells through induction of lethal oxidative and mitochondriotoxic stress. Cancers 11:590

    Article  CAS  PubMed Central  Google Scholar 

  32. Ji HW, Kim H, Kim HW et al (2020) Genome-wide comparison of the target genes of the reactive oxygen species and non-reactive oxygen species constituents of cold atmospheric plasma in cancer cells. Cancers 12(9):2640

    Article  CAS  PubMed Central  Google Scholar 

  33. Justiniano R, de Faria LL, Perer J et al (2021) The endogenous tryptophan-derived photoproduct 6-formylindolo [3,2-b] carbazole (FICZ) is a nanomolar photosensitizer that can be harnessed for the photodynamic elimination of skin cancer cells in vitro and in vivo. Photochem Photobiol 97:180–191

    Article  CAS  PubMed  Google Scholar 

  34. Tang H, Kong Y, Guo J et al (2013) Diallyl disulfide suppresses proliferation and induces apoptosis in human gastric cancer through Wnt-1 signaling pathway by up-regulation of miR-200b and miR-22. Cancer Lett 340:72–81

    Article  CAS  PubMed  Google Scholar 

  35. Huang J, Yang B, Xiang T et al (2015) Diallyl disulfide inhibits growth and metastatic potential of human triple-negative breast cancer cells through inactivation of the beta-catenin signaling pathway. Mol Nutr Food Res 59:1063–1075

    Article  CAS  PubMed  Google Scholar 

  36. Bond M, Fabunmi RP, Baker AH et al (1998) Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-kappa B. FEBS Lett 435:29–34

    Article  CAS  PubMed  Google Scholar 

  37. Lee SJ, Cho SC, Lee EJ et al (2013) Interleukin-20 promotes migration of bladder cancer cells through extracellular signal-regulated kinase (ERK)-mediated MMP-9 protein expression leading to nuclear factor (NF-kappaB) activation by inducing the up-regulation of p21(WAF1) protein expression. J Biol Chem 288:5539–5552

    Article  CAS  PubMed  Google Scholar 

  38. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. Cancer J Clin 68:7–30

    Article  Google Scholar 

  39. Siegel RL, Miller KD, Jemal A (2020) Cancer statistics, 2020. Cancer J Clin 70:7–30

    Article  Google Scholar 

  40. Kassahun WT (2015) Unresolved issues and controversies surrounding the management of colorectal cancer liver metastasis. World J Surg Oncol 13:61

    Article  PubMed  PubMed Central  Google Scholar 

  41. Fatemi SR, Pourhoseingholi MA, Asadi F et al (2015) Recurrence and five-year survival in colorectal cancer patients after surgery. Iran J Cancer Prev 8:e3439

    Article  PubMed  PubMed Central  Google Scholar 

  42. Park J, Cho J, Song EJ (2020) Ubiquitin-proteasome system (UPS) as a target for anticancer treatment. Arch Pharm Res 43:1144–1161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Monteith BE, Venner CP, Reece DE et al (2020) Drug-induced thrombotic microangiopathy with concurrent proteasome inhibitor use in the treatment of multiple myeloma: a case series and review of the literature. Clin Lymphoma Myeloma Leuk 20:e791–e800

    Article  PubMed  Google Scholar 

  44. Tundo GR, Sbardella D, Santoro AM et al (2020) The proteasome as a druggable target with multiple therapeutic potentialities: cutting and non-cutting edges. Pharmacol Ther 213:107579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Fan Q, Liu B (2017) Identification of the anticancer effects of a novel proteasome inhibitor, ixazomib, on colorectal cancer using a combined method of microarray and bioinformatics analysis. Onco Targets Ther 10:3591–3606

    Article  PubMed  PubMed Central  Google Scholar 

  46. Yang ES, Nassar AH, Adib E et al (2021) Gene expression signature correlates with outcomes in metastatic renal cell carcinoma patients treated with everolimus alone or with a vascular disrupting agent. Mol Cancer Ther 20:1454–1461

    Article  CAS  PubMed  Google Scholar 

  47. Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin 71:209–249

    Article  Google Scholar 

  48. Shen S, Wei C, Fu J (2021) RNA-sequencing reveals heat shock 70-kDa protein 6 (HSPA6) as a novel thymoquinone-upregulated gene that inhibits growth, migration, and invasion of triple-negative breast cancer cells. Front Oncol 11:667995

    Article  PubMed  PubMed Central  Google Scholar 

  49. Shanmugam MK, Arfuso F, Kumar AP et al (2018) Modulation of diverse oncogenic transcription factors by thymoquinone, an essential oil compound isolated from the seeds of Nigella sativa Linn. Pharmacol Res 129:357–364

    Article  CAS  PubMed  Google Scholar 

  50. Khan MA, Tania M, Fu J (2019) Epigenetic role of thymoquinone: impact on cellular mechanism and cancer therapeutics. Drug Discov Today 24:2315–2322

    Article  CAS  PubMed  Google Scholar 

  51. Li J, Khan MA, Wei C et al (2017) Thymoquinone inhibits the migration and invasive characteristics of cervical cancer cells SiHa and CaSki in vitro by targeting epithelial to mesenchymal transition associated transcription factors twist1 and zeb1. Molecules 22(12):2105

    Article  PubMed Central  Google Scholar 

  52. Zhou J, Imani S, Shasaltaneh MD et al (2021) PIK3CA hotspot mutations p. H1047R and p. H1047L sensitize breast cancer cells to thymoquinone treatment by regulating the PI3K/Akt1 pathway. Mol Biol Rep 49(3):1799–1816

    Article  PubMed  Google Scholar 

  53. 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. Int J Med Sci 12:256–263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wang DW, Tang JY, Zhang GQ et al (2020) ARHGEF10L expression regulates cell proliferation and migration in gastric tumorigenesis. Biosci Biotechnol Biochem 84:1362–1372

    Article  CAS  PubMed  Google Scholar 

  55. Wang L, Hou J, Wang J et al (2020) Regulatory roles of HSPA6 in Actinidia chinensis Planch. Root extract (acRoots)-inhibited lung cancer proliferation. Clin Transl Med 10(2):e46

    Article  PubMed  PubMed Central  Google Scholar 

  56. Noonan EJ, Place RF, Giardina C et al (2007) Hsp70B′ regulation and function. Cell Stress Chaperones 12:393–402

    Article  PubMed  PubMed Central  Google Scholar 

  57. Lim SO, Park SG, Yoo JH et al (2005) Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules. World J Gastroenterol 11:2072–2079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Cui N, Xu Y, Cao Z et al (2013) Effects of heat stress on the level of heat shock protein 70 on the surface of hepatocellular carcinoma Hep G2 cells: implications for the treatment of tumors. Tumour Biol 34:743–748

    Article  CAS  PubMed  Google Scholar 

  59. Coto-Llerena M, Tosti N, Taha-Mehlitz S et al (2021) Transcriptional enhancer factor domain family member 4 exerts an oncogenic role in hepatocellular carcinoma by hippo-independent regulation of heat shock protein 70 family members. Hepatol Commun 5:661–674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Guo X, Wang Y, Zhang H et al (2020) Identification of the prognostic value of immune-related genes in esophageal cancer. Front Genet 11:989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wang L, Wei Q, Zhang M et al (2020) Identification of the prognostic value of immune gene signature and infiltrating immune cells for esophageal cancer patients. Int Immunopharmacol 87:106795

    Article  CAS  PubMed  Google Scholar 

  62. Chen H, Luo J, Guo J (2020) Construction and validation of a 7-immune gene model for prognostic assessment of esophageal carcinoma. Med Sci Monit 26:e927392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Zhu C, Xia Q, Gu B et al (2021) Esophageal cancer associated immune genes as biomarkers for predicting outcome in upper gastrointestinal tumors. Front Genet 12:707299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Trepel J, Mollapour M, Giaccone G et al (2010) Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer 10:537–549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Johnson JL (2021) Mutations in Hsp90 cochaperones result in a wide variety of human disorders. Front Mol Biosci 8:787260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Workman P, Burrows F, Neckers L et al (2007) Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Ann N.Y. Acad Sci 1113:202–216

    Article  CAS  PubMed  Google Scholar 

  67. Modi S, Stopeck A, Linden H et al (2011) HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clin Cancer Res 17:5132–5139

    Article  CAS  PubMed  Google Scholar 

  68. Ma L, Sato F, Sato R et al (2014) Dual targeting of heat shock proteins 90 and 70 promotes cell death and enhances the anticancer effect of chemotherapeutic agents in bladder cancer. Oncol Rep 31:2482–2492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kuballa P, Baumann AL, Mayer K et al (2015) Induction of heat shock protein HSPA6 (HSP70B′) upon HSP90 inhibition in cancer cell lines. FEBS Lett 589:1450–1458

    Article  CAS  PubMed  Google Scholar 

  70. Ramirez VP, Stamatis M, Shmukler A et al (2015) Basal and stress-inducible expression of HSPA6 in human keratinocytes is regulated by negative and positive promoter regions. Cell Stress Chaperones 20:95–107

    Article  CAS  PubMed  Google Scholar 

  71. Tukaj S (2020) Heat shock protein 70 as a double agent acting inside and outside the cell: insights into autoimmunity. Int J Mol Sci 21(15):5298

    Article  CAS  PubMed Central  Google Scholar 

  72. Sojka DR, Hasterok S, Vydra N et al (2021) Inhibition of the heat shock protein a (HSPA) family potentiates the anticancer effects of manumycin a. Cells 10:1418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Sojka DR, Hasterok S, Vydra N et al (2021) Inhibition of the heat shock protein a (HSPA) family potentiates the anticancer effects of manumycin a. Cells 10(6):1418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Mofers A, Selvaraju K, Gubat J et al (2020) Identification of proteasome inhibitors using analysis of gene expression profiles. Eur J Pharmacol 889:173709

    Article  CAS  PubMed  Google Scholar 

  75. Court KA, Hatakeyama H, Wu SY et al (2017) HSP70 inhibition synergistically enhances the effects of magnetic fluid hyperthermia in ovarian cancer. Mol Cancer Ther 16:966–976

    Article  CAS  PubMed  Google Scholar 

  76. Sun H, Zou HY, Cai XY et al (2020) Network analyses of the differential expression of heat shock proteins in glioma. DNA Cell Biol 39:1228–1242

    Article  CAS  PubMed  Google Scholar 

  77. Feng R, Chao K, Chen SL et al (2018) Heat shock protein family A member 6 combined with clinical characteristics for the differential diagnosis of intestinal Behcet’s disease. J Dig Dis 19:350–358

    Article  CAS  PubMed  Google Scholar 

  78. Li CJ, Ning W, Matthay MA et al (2007) MAPK pathway mediates EGR-1-HSP70-dependent cigarette smoke-induced chemokine production. Am J Physiol Lung Cell Mol Physiol 292:L1297–L1303

    Article  CAS  PubMed  Google Scholar 

  79. Regeling A, Imhann F, Volders HH 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. Biochim Biophys Acta 1862:788–796

    Article  CAS  PubMed  Google Scholar 

  80. Su YS, Hwang LH, Chen CJ (2021) Heat shock protein A6, a novel HSP70, is induced during enterovirus A71 infection to facilitate internal ribosomal entry site-mediated translation. Front Microbiol 12:664955

    Article  PubMed  PubMed Central  Google Scholar 

  81. Gliozzi M, Scicchitano M, Bosco F et al (2019) Modulation of nitric oxide synthases by oxidized LDLs: role in vascular inflammation and atherosclerosis development. Int J Mol Sci 20:3294

    Article  CAS  PubMed Central  Google Scholar 

  82. Grootaert MOJ, Moulis M, Roth L et al (2018) Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis. Cardiovasc Res 114:622–634

    Article  CAS  PubMed  Google Scholar 

  83. Forstermann U, Sessa WC (2012) Nitric oxide synthases: regulation and function. Eur Heart J 33(829–37):37a–37d

    Google Scholar 

  84. McCullagh KJ, Cooney R, O’Brien T (2016) Endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B′) in human arterial smooth muscle cells. Nitric Oxide 52:41–48

    Article  CAS  PubMed  Google Scholar 

  85. Takagi Y, Aoki T, Takahashi JC et al (2014) Differential gene expression in relation to the clinical characteristics of human brain arteriovenous malformations. Neurol Med Chir 54:163–175

    Article  Google Scholar 

  86. Fa J, Zhang X, Zhang X et al (2021) Long noncoding RNA lnc-TSSK2-8 activates canonical Wnt/beta-catenin signaling through small heat shock proteins HSPA6 and CRYAB. Front Cell Dev Biol 9:660576

    Article  PubMed  PubMed Central  Google Scholar 

  87. Wu K, Zhao Q, Li Z et al (2018) Bioinformatic screening for key miRNAs and genes associated with myocardial infarction. FEBS Open Bio 8:897–913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Swinkels M, Rijkers M, Voorberg J et al (2018) Emerging concepts in immune thrombocytopenia. Front Immunol 9:880

    Article  PubMed  PubMed Central  Google Scholar 

  89. Liu SY, Yuan D, Sun RJ et al (2021) Significant reductions in apoptosis-related proteins (HSPA6, HSPA8, ITGB3, YWHAH, and PRDX6) are involved in immune thrombocytopenia. J Thromb Thrombolysis 51:905–914

    Article  CAS  PubMed  Google Scholar 

  90. Shervington L, Darekar A, Shaikh M et al (2018) Identifying reliable diagnostic/predictive biomarkers for rheumatoid arthritis. Biomark Insights 13:1177271918801005

    Article  PubMed  PubMed Central  Google Scholar 

  91. Duncan EJ, Cheetham ME, Chapple JP et al (2015) The role of HSP70 and its co-chaperones in protein misfolding, aggregation and disease. Subcell Biochem 78:243–273

    Article  CAS  PubMed  Google Scholar 

  92. Becirovic L, Brown IR (2017) Targeting of heat shock protein HSPA6 (HSP70B′) to the periphery of nuclear speckles is disrupted by a transcription inhibitor following thermal stress in human neuronal cells. Neurochem Res 42:406–414

    Article  CAS  PubMed  Google Scholar 

  93. Deane CAS, Brown IR (2017) Differential targeting of Hsp70 heat shock proteins HSPA6 and HSPA1A with components of a protein disaggregation/refolding machine in differentiated human neuronal cells following thermal stress. Front Neurosci 11:227

    Article  PubMed  PubMed Central  Google Scholar 

  94. Deane CAS, Brown IR (2018) Knockdown of heat shock proteins HSPA6 (Hsp70B′) and HSPA1A (Hsp70-1) sensitizes differentiated human neuronal cells to cellular stress. Neurochem Res 43:340–350

    Article  CAS  PubMed  Google Scholar 

  95. Chiricosta L, Gugliandolo A, Bramanti P et al (2020) Could the heat shock proteins 70 family members exacerbate the immune response in multiple sclerosis? An in silico study. Genes 11:615

    Article  CAS  PubMed Central  Google Scholar 

  96. Jain CV, Jessmon P, Barrak CT et al (2017) Trophoblast survival signaling during human placentation requires HSP70 activation of MMP2-mediated HBEGF shedding. Cell Death Differ 24:1772–1783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Matsumaru D, Murashima A, Fukushima J et al (2015) Systematic stereoscopic analyses for cloacal development: the origin of anorectal malformations. Sci Rep 5:13943

    Article  PubMed  PubMed Central  Google Scholar 

  98. Al-Qattan MM (2021) The classification of VACTERL association into 3 groups according to the limb defect. Plast Reconstr Surg Glob Open 9:e3360

    Article  PubMed  PubMed Central  Google Scholar 

  99. Kause F, Zhang R, Ludwig M et al (2019) HSPA6: a new autosomal recessive candidate gene for the VATER/VACTERL malformation spectrum. Birth Defects Res 111:591–597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Goodman SC, Letra A, Dorn S et al (2014) Expression of heat shock proteins in periapical granulomas. J Endod 40:830–836

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank people from Key Laboratory of Epigenetics and Oncology, Research Center for Preclinical Medicine, Southwest Medical University.

Funding

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81672887, 82073263, and 81172049).

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  1. Binghui Song, Shiyi Shen and Shangyi Fu have contributed equally to this work.

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  1. Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China

    Binghui Song, Shiyi Shen & Junjiang Fu

  2. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Shangyi Fu

  3. School of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA

    Shangyi Fu

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JF designed and supervised the project. SS wrote the manuscript. BS, SF, JF wrote and edited the manuscript. All authors contributed and approved the submitted version.

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Song, B., Shen, S., Fu, S. et al. HSPA6 and its role in cancers and other diseases. Mol Biol Rep 49, 10565–10577 (2022). https://doi.org/10.1007/s11033-022-07641-5

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