Association of the Epithelial-Mesenchymal Transition (EMT) with Cisplatin Resistance

Int J Mol Sci. 2020 Jun 3;21(11):4002. doi: 10.3390/ijms21114002.


Therapy resistance is a characteristic of cancer cells that significantly reduces the effectiveness of drugs. Despite the popularity of cisplatin (CP) as a chemotherapeutic agent, which is widely used in the treatment of various types of cancer, resistance of cancer cells to CP chemotherapy has been extensively observed. Among various reported mechanism(s), the epithelial-mesenchymal transition (EMT) process can significantly contribute to chemoresistance by converting the motionless epithelial cells into mobile mesenchymal cells and altering cell-cell adhesion as well as the cellular extracellular matrix, leading to invasion of tumor cells. By analyzing the impact of the different molecular pathways such as microRNAs, long non-coding RNAs, nuclear factor-κB (NF-ĸB), phosphoinositide 3-kinase-related protein kinase (PI3K)/Akt, mammalian target rapamycin (mTOR), and Wnt, which play an important role in resistance exhibited to CP therapy, we first give an introduction about the EMT mechanism and its role in drug resistance. We then focus specifically on the molecular pathways involved in drug resistance and the pharmacological strategies that can be used to mitigate this resistance. Overall, we highlight the various targeted signaling pathways that could be considered in future studies to pave the way for the inhibition of EMT-mediated resistance displayed by tumor cells in response to CP exposure.

Keywords: cancer therapy; chemoresistance; cisplatin; epithelial–mesenchymal transition (EMT); signal transduction.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Differentiation
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Epithelial-Mesenchymal Transition / drug effects*
  • Forkhead Box Protein O1 / metabolism
  • Humans
  • MicroRNAs / metabolism
  • NF-kappa B / metabolism
  • Neoplasms / drug therapy
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism


  • Antineoplastic Agents
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • MicroRNAs
  • NF-kappa B
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Cisplatin