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Review
. 2020 Jun 3;21(11):4002.
doi: 10.3390/ijms21114002.

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

Milad Ashrafizadeh  1 , Ali Zarrabi  2   3 , Kiavash Hushmandi  4   5 , Mahshad Kalantari  6 , Reza Mohammadinejad  7 , Tahereh Javaheri  8 , Gautam Sethi  9
Affiliations
Review

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

Milad Ashrafizadeh et al. Int J Mol Sci. .

Abstract

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.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The involvement of different molecular pathways in anticancer actions of cisplatin (CP).
Figure 2
Figure 2
A summary of selected molecular pathways regulating epithelial–mesenchymal transition (EMT) and their possible involvement in resistance to CP therapy. mTOR, mammalian target of rapamycin; Akt, protein kinase B; GSK-3β, glycogensynthase kinase-3β; miR, microRNA; PTP1B, protein tyrosine phosphatase 1B; HOXA3, homeobox A3; Mdm2, mouse double minute 2 homolog; IKKβ, Inhibitor of NF-κB kinase subunit β; ZEB, zinc-finger E-box binding homeobox; lncRNA, long non-coding RNA; UCA1, urogenital carcinoma antigen 1; elF5A2, eukaryotic initiation factor 5A2.
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