S100A7 promotes the migration, invasion and metastasis of human cervical cancer cells through epithelial-mesenchymal transition

Oncotarget. 2017 Apr 11;8(15):24964-24977. doi: 10.18632/oncotarget.15329.

Abstract

S100A7 is an EF-hand calcium-binding protein that has been suggested to be implicated in cell proliferation, migration, invasion and tumor metastasis. However, its role in cervical cancer has not yet been fully clarified. The present study used immunohistochemistry analysis of S100A7 in clinical specimens of cervical cancer to show that S100A7 expression was significantly upregulated in cervical cancer tissues compared with normal cervical tissues and S100A7 expression in high grade cervical intraepithelial neoplasm (CIN) was significantly higher than cervical cancer. Statistical analysis showed that S100A7 expression was associated with tumor grade (P <0.01) and lymph node metastasis (P <0.05). Functional studies showed that overexpression of S100A7 in cervical cancer cells promoted migration, invasion and metastasis of cervical cancer cells without influencing cell proliferation. Furthermore, S100A7 was found to be secreted into the conditioned media and extracellular S100A7 enhanced cell migration and invasion. Mechanistically, S100A7 bound to RAGE and activated ERK signaling pathway. And S100A7 enhanced cell mesenchymal properties and induced epithelial-mesenchymal transition. In summary, these data reveal a crucial role for S100A7 in regulating cell migration, invasion, metastasis and EMT of cervical cancer and suggest that targeting S100A7 may offer a new targeted strategy for cervical cancer.

Keywords: EMT; S100A7; cervical cancer; invasion; metastasis.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Epithelial-Mesenchymal Transition
  • Female
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • S100 Calcium Binding Protein A7 / biosynthesis
  • S100 Calcium Binding Protein A7 / genetics
  • S100 Calcium Binding Protein A7 / metabolism*
  • Transfection
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • S100 Calcium Binding Protein A7
  • S100A7 protein, human