DNA polymerase iota (Pol ι) promotes the migration and invasion of breast cancer cell via EGFR-ERK-mediated epithelial to mesenchymal transition

Cancer Biomark. 2019;24(3):363-370. doi: 10.3233/CBM-181516.

Abstract

Background and objective: Dysregulation of DNA polymerase iota (Pol ι) in breast cancer might contribute to the accumulation of genomic mutations and promotes breast cancer progression. In this study we explored the clinical relevance and biological function of Pol ι in breast cancer.

Methods: qRT-PCR was used to determine the expression levels of Pol ι in 31 breast cancer tissues. Then the stable overexpression of Pol ι and knockdown of Pol ι breast cancer cell lines were constructed. Wound-healing assay and transwell assay were performed to evaluate cell migratory and invasiveness, respectively. Signaling pathway was analyzed by western blot.

Results: The expression levels of Pol ι is overexpressed in breast cancer tissues and significantly higher in breast cancer tissues with lymph node metastasis compared to those without lymph node metastasis. Elevated Pol ι expression promoted migratory and invasiveness of breast cancer cells. Signaling pathway analysis indicated EGFR-ERK cascade works as a mediator of Pol ι-induced EMT of breast cancer cells.

Conclusions: These data demonstrate the underlying mechanism by which Pol ι promotes breast cancer progression, suggesting that Pol ι may be a potential therapeutic target against breast cancer.

Keywords: Breast cancer; EGFR; EMT; Pol ι; metastasis.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • DNA Polymerase iota
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Epithelial-Mesenchymal Transition* / genetics
  • ErbB Receptors / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Staging
  • Signal Transduction

Substances

  • EGFR protein, human
  • ErbB Receptors
  • Extracellular Signal-Regulated MAP Kinases
  • DNA-Directed DNA Polymerase
  • DNA Polymerase iota
  • POLI protein, human