DNAJB6 Promotes Ferroptosis in Esophageal Squamous Cell Carcinoma

Dig Dis Sci. 2020 Jul;65(7):1999-2008. doi: 10.1007/s10620-019-05929-4. Epub 2019 Nov 8.

Abstract

Background: DnaJ/Hsp40 homolog, subfamily B, member 6 (DNAJB6) is significantly down-regulated in esophageal squamous cell carcinoma (ESCC), while its complicated molecular mechanisms are still unknown.

Aims: To investigate the relationship between DNAJB6 and ESCC.

Methods: The expression of DNAJB6 was detected in ESCC patient by Western blot and immunohistochemistry. To overexpress DNAJB6a by lentivirus infection, colony-forming, CCK-8, transwell, mouse xenograft assays were utilized to verify the proliferous, invasive, and migratory role of DNAJB6a in ESCC cells. The MDA and GSH assays determine whether DNAJB6a participates in cell redox reaction. The variation of AKT and GPX4 was detected by Western blot.

Results: The correlation between DNAJB6 level and lymph node metastasis in ESCC patient was negative. Overexpressing DNAJB6a shows tumor-suppressive effects in vitro and in vivo. In addition, DNAJB6a overexpression was accompanied together with a remarkable reduction in the protein levels of GPX4 and phosphorylated AKT (p-AKT).

Conclusion: DNAJB6 plays an important anti-oncogenic role in ESCC evolvement via ferroptosis.

Keywords: AKT; DNAJB6; ESCC; Ferroptosis; GPX4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / genetics*
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Ferroptosis / genetics
  • Glutathione / metabolism
  • HSP40 Heat-Shock Proteins / genetics*
  • HSP40 Heat-Shock Proteins / metabolism
  • Humans
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Mitochondria / ultrastructure
  • Molecular Chaperones / genetics*
  • Molecular Chaperones / metabolism
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Oxidation-Reduction
  • Phospholipid Hydroperoxide Glutathione Peroxidase / metabolism
  • Protein Isoforms / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNAJB6 protein, human
  • HSP40 Heat-Shock Proteins
  • Molecular Chaperones
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Proto-Oncogene Proteins c-akt
  • Glutathione