PIBF1 suppresses the ATR/CHK1 signaling pathway and promotes proliferation and motility of triple-negative breast cancer cells

Breast Cancer Res Treat. 2020 Aug;182(3):591-600. doi: 10.1007/s10549-020-05732-0. Epub 2020 Jun 11.

Abstract

Purpose: This study evaluates the oncogenic role of PIBF1 in triple-negative breast cancer (TNBC). TNBC is considered to have a poorer prognosis than other types of breast cancer and is associated with high risk of recurrence and distant metastasis. Currently, there are no effective therapies for the TNBC patients with distant metastasis due to the lack of targeted therapeutic options.

Methods: The effects of PIBF1 knockdown on the cell viability and motility of TNBC cell lines were investigated. Effects of PIBF1 overexpression on tumorigenicity and cell motility were confirmed using Ba/F3 cell line and xenograft study on BALB/c nude mice.

Results: In TNBC cell lines that highly express PIBF1, knockdown of PIBF1 induces apoptosis and suppresses cell viability and motility with activation of the ATR/CHK1 signaling pathway. Moreover, the oncogenic function of PIBF1 was confirmed using the Ba/F3 cell line.

Conclusion: For the first time, these findings clarify the role of PIBF1 in regulating ATR/CHK1 signaling pathway and inhibiting the proliferation and migration of TNBC cell lines. These results demonstrate the oncogenic roles of PIBF1 and provide new insights into the function and the molecular mechanism of PIBF1 in malignant TNBC.

Keywords: ATR/CHK1 signaling pathway; Motility; PIBF1; Proliferation; TNBC.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Ataxia Telangiectasia Mutated Proteins / antagonists & inhibitors*
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Checkpoint Kinase 1 / antagonists & inhibitors*
  • Checkpoint Kinase 1 / metabolism
  • Female
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Pregnancy Proteins / biosynthesis
  • Pregnancy Proteins / genetics
  • Pregnancy Proteins / metabolism*
  • Signal Transduction
  • Suppressor Factors, Immunologic / biosynthesis
  • Suppressor Factors, Immunologic / genetics
  • Suppressor Factors, Immunologic / metabolism*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • PIBF1 protein, human
  • Pregnancy Proteins
  • Suppressor Factors, Immunologic
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • CHEK1 protein, human
  • Checkpoint Kinase 1