Overexpression of IL-8 promotes cell migration via PI3K-Akt signaling pathway and EMT in triple-negative breast cancer

Pathol Res Pract. 2021 Jul:223:152824. doi: 10.1016/j.prp.2020.152824. Epub 2020 Jun 20.

Abstract

Triple-negative breast cancer (TNBC) is a type of malignant and heterogeneous tumor in premenopausal females with ineffective therapeutic targets. IL-8 is one of the earliest discovered chemotaxis cytokines which expression is closely related to the progress of various cancers. Previous studies show that IL-8 determines the prognosis of TNBC patients, nevertheless how IL-8 influence the progress of TNBC is unclear. In our studies, we discovered that overexpression of IL-8 promotes TNBC cells (TNBCs) migration and tumor growth via the PI3K-Akt and MAPK signaling pathway. Cell-cycle of TNBCs arrest at S phase by overexpression of IL-8, however, there is no significant difference on the cell viability and cell apoptosis of TNBCs. Besides, overexpression of IL-8 result in the downregulation of E-cadherin and the upregulation of Cyclin B1 in MDA-MB-231 cells. Taken together, our results suggest that IL-8 plays a crucial role in the progress of TNBC, and it could be a novel therapeutic target of TNBC.

Keywords: IL-8; Migration; TNBC; Tumorigenesis.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • S Phase Cell Cycle Checkpoints
  • Signal Transduction
  • Triple Negative Breast Neoplasms / enzymology*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Burden
  • Up-Regulation

Substances

  • CXCL8 protein, human
  • Interleukin-8
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt