Livin promotes the progression and metastasis of breast cancer through the regulation of epithelial‑mesenchymal transition via the p38/GSK3β pathway

Oncol Rep. 2017 Dec;38(6):3574-3582. doi: 10.3892/or.2017.6017. Epub 2017 Oct 10.


Epithelial-mesenchymal transition (EMT) plays a pivotal role in the invasion and metastasis of breast cancer. Livin is a recently identified member of the inhibitors of the apoptosis protein family, which has been revealed to facilitate the progression of several types of cancer. However, the role of Livin in EMT and metastasis of breast cancer and its underlying mechanisms are not fully elucidated. In the present study, the levels of Livin mRNA and protein expression were found to be elevated in breast cancer tissues and cell lines. In addition, Livin expression was positively correlated with TNM stage and lymph node metastasis in total and triple-negative breast cancer (TNBC) cases. Livin overexpression enhanced the migratory and invasive abilities of the MCF-7 cells, accompanied by increases in vimentin, N-cadherin, Snail, MMP-2 and MMP-7 and a decrease in E-cadherin. Conversely, the downregulation of Livin had the opposite effect in MDA-MB-231 cells. Furthermore, the upregulation of Livin expression markedly stimulated the activation of the p38/GSK3β pathway, while the downregulation of Livin expression clearly suppressed the activation of the p38/GSK3β pathway. In conclusion, our results revealed that Livin induced EMT through the activation of the p38/GSK3β pathway, which in turn promoted the progression and metastasis of breast cancer, especially for TNBC.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Apoptosis
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 beta / genetics*
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • MAP Kinase Signaling System / genetics
  • MCF-7 Cells
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Staging
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology
  • p38 Mitogen-Activated Protein Kinases / genetics*


  • Adaptor Proteins, Signal Transducing
  • BIRC7 protein, human
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • p38 Mitogen-Activated Protein Kinases