Acquisition of epithelial-mesenchymal transition is associated with Skp2 expression in paclitaxel-resistant breast cancer cells

Br J Cancer. 2014 Apr 15;110(8):1958-67. doi: 10.1038/bjc.2014.136. Epub 2014 Mar 18.


Background: Breast cancer is the most common female malignant disease, and the second leading cause of cancer-related death in the United States. Acquired resistance to chemotherapeutic drugs is a pivotal reason that leads to worse treatment outcome of breast cancer. Therefore, it is urgent to elucidate the mechanism of drug resistance in breast cancer.

Methods: To investigate the underlying molecular basis of the acquired resistant cells to paclitaxel in breast cancer, we used multiple methods including real-time RT-PCR, western blotting analysis, migration and invasion assays, wound healing assay, and transfection.

Results: We found that epithelial-mesenchymal transition (EMT) is involved in paclitaxel-resistant (PR) breast cancer cells. The resistant cells with EMT features exhibit increased migration and invasion activities. Mechanistically, high expression of Skp2 was found to be associated with EMT in PR cells. Notably, depletion of Skp2 in PR cells led to partial reversal of EMT phenotype.

Conclusions: These findings suggest that Skp2 was critically involved in PR-mediated EMT. Skp2 could be a potential therapeutic target for breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • Paclitaxel / administration & dosage*
  • S-Phase Kinase-Associated Proteins / biosynthesis
  • S-Phase Kinase-Associated Proteins / genetics*
  • United States


  • S-Phase Kinase-Associated Proteins
  • Paclitaxel