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Review

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

1
Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran
2
Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, Istanbul 34956, Turkey
3
Center of Excellence for Functional Surfaces and Interfaces (EFSUN), Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla, Istanbul 34956, Turkey
4
Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran 1417414418, Iran
5
Kazerun Health Technology Incubator, Shiraz University of Medical Sciences, Shiraz 1433671348, Iran
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Department of Genetic Science, Tehran Medical Science Branch, Islamic Azad University, Tehran 19168931813, Iran
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Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman 1355576169, Iran
8
Health Informatics Lab, Metropolitan College, Boston University, Boston, MA 02215, USA
9
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(11), 4002; https://doi.org/10.3390/ijms21114002
Received: 13 April 2020 / Revised: 14 May 2020 / Accepted: 26 May 2020 / Published: 3 June 2020
(This article belongs to the Special Issue Cisplatin in Cancer Therapy: Molecular Mechanisms of Action 2.0)
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. View Full-Text
Keywords: cisplatin; cancer therapy; chemoresistance; epithelial–mesenchymal transition (EMT); signal transduction cisplatin; cancer therapy; chemoresistance; epithelial–mesenchymal transition (EMT); signal transduction
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MDPI and ACS Style

Ashrafizadeh, M.; Zarrabi, A.; Hushmandi, K.; Kalantari, M.; Mohammadinejad, R.; Javaheri, T.; Sethi, G. Association of the Epithelial–Mesenchymal Transition (EMT) with Cisplatin Resistance. Int. J. Mol. Sci. 2020, 21, 4002. https://doi.org/10.3390/ijms21114002

AMA Style

Ashrafizadeh M, Zarrabi A, Hushmandi K, Kalantari M, Mohammadinejad R, Javaheri T, Sethi G. Association of the Epithelial–Mesenchymal Transition (EMT) with Cisplatin Resistance. International Journal of Molecular Sciences. 2020; 21(11):4002. https://doi.org/10.3390/ijms21114002

Chicago/Turabian Style

Ashrafizadeh, Milad, Ali Zarrabi, Kiavash Hushmandi, Mahshad Kalantari, Reza Mohammadinejad, Tahereh Javaheri, and Gautam Sethi. 2020. "Association of the Epithelial–Mesenchymal Transition (EMT) with Cisplatin Resistance" International Journal of Molecular Sciences 21, no. 11: 4002. https://doi.org/10.3390/ijms21114002

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