Possible involvement of TGF‑β‑SMAD‑mediated epithelial‑mesenchymal transition in pro‑metastatic property of PAX6

Oncol Rep. 2020 Aug;44(2):555-564. doi: 10.3892/or.2020.7644. Epub 2020 Jun 11.


Paired box 6 (PAX6) is a transcription factor that has oncogenic features. In breast cancer, PAX6 facilitates tumor progression; however, the underlying mechanism is largely unknown. The majority of breast cancer‑related mortalities are associated with metastasis of cancer cells. Therefore, the present study aimed to investigate the role of PAX6 in breast tumor metastasis. PAX6 was stably overexpressed in breast cancer cells to perform tumor migration and metastasis assays in vitro and in vivo. In addition, the expression of PAX6 and transforming growth factor β (TGF‑β)‑SMAD signaling associated proteins on human breast cancer tissue array, as well as key factors involved in epithelial‑mesenchymal transition (EMT) were assayed to explore the mechanism underlying metastasis of breast cancer cells. The expression levels of PAX6 were demonstrated to be increased in human breast cancer tissues and associated with poor clinical outcomes. Overexpression of PAX6 markedly promoted metastasis. Further investigation revealed that PAX6 overexpression increased TGF‑β‑SMAD signaling pathway and induced EMT. These results suggested that highly expressed PAX6 led to EMT through TGF‑β‑SMAD signaling pathway, thereby promoting cell metastasis and ultimately affecting survival in patients with breast cancer. Taken together, findings indicated that PAX6 may serve as a therapeutic target for the clinical treatment of breast cancer and the underlying mechanism could be used to overcome metastasis of cancer cells.

Keywords: MCF7; MDA-MB-231; migration and invasion; epithelial-mesenchymal transition; zebrafish.

MeSH terms

  • Animals
  • Breast / pathology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Datasets as Topic
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Neoplasm Metastasis / genetics
  • PAX6 Transcription Factor / metabolism*
  • Prognosis
  • Signal Transduction / genetics
  • Smad Proteins / metabolism
  • Tissue Array Analysis
  • Transforming Growth Factor beta
  • Xenograft Model Antitumor Assays
  • Zebrafish


  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Smad Proteins
  • Transforming Growth Factor beta