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Review
. 2016 Jul 22;21(7):965.
doi: 10.3390/molecules21070965.

Targeting Epithelial-Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer

Bowen Du  1 , Joong Sup Shim  2
Affiliations
Review

Targeting Epithelial-Mesenchymal Transition (EMT) to Overcome Drug Resistance in Cancer

Bowen Du et al. Molecules. .

Abstract

Epithelial-mesenchymal transition (EMT) is known to play an important role in cancer progression, metastasis and drug resistance. Although there are controversies surrounding the causal relationship between EMT and cancer metastasis, the role of EMT in cancer drug resistance has been increasingly recognized. Numerous EMT-related signaling pathways are involved in drug resistance in cancer cells. Cells undergoing EMT show a feature similar to cancer stem cells (CSCs), such as an increase in drug efflux pumps and anti-apoptotic effects. Therefore, targeting EMT has been considered a novel opportunity to overcome cancer drug resistance. This review describes the mechanism by which EMT contributes to drug resistance in cancer cells and summarizes new advances in research in EMT-associated drug resistance.

Keywords: cancer stem cells; chemotherapy; drug resistance; epithelial–mesenchymal transition.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Diverse signaling pathways associated with epithelial–mesenchymal transition (EMT). Transforming growth factor beta (TGFβ) signals activate SMAD2 and SMAD3 that complex with SMAD4. The trimeric SMAD complex enters the nucleus and leads to the transcription of EMT transcription factors (EMT-TFs) [9]. Activation of Wnt signaling inhibits the destruction complex containing glycogen synthase kinase 3 beta (GSK-3β) through Disheveled (DSH), facilitating β-catenin to enter the nucleus and activate the Snail transcription [10]. Notch receptors can be activated by binding to Delta and Jagged ligands. After activation, Notch intracellular domain (Notch-IC) is released through a cascade of proteolytic cleavages and activates CSL transcription factor to express EMT-TFs [11]. In Sonic Hedgehog (SHH) signaling, ligand binding to Patched 1 (PTCH1) receptors activates Smoothened (SMO) and Glioma (GLI) family transcription factors that induce Snail expression [12]. Interleukin-6 (IL-6) can induce Snail expression by activating STAT3 [13].
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