Interplay of EMT and CSC in Cancer and the Potential Therapeutic Strategies.

Shihori Tanabe,Horacio Cabral,Sabina Quader,Ryuichi Ono

doi:10.3389/fphar.2020.00904

Abstract

The mechanism of epithelial-mesenchymal transition (EMT) consists of the cellular phenotypic transition from epithelial to mesenchymal status. The cells exhibiting EMT exist in cancer stem cell (CSC) population, which is involved in drug resistance. CSCs demonstrating EMT feature remain after cancer treatment, which leads to drug resistance, recurrence, metastasis and malignancy of cancer. In this context, the recent advance of nanotechnology in the medical application has ascended the possibility to target CSCs using nanomedicines. In this review article, we focused on the mechanism of CSCs and EMT, especially into the signaling pathways in EMT, regulation of EMT and CSCs by microRNAs and nanomedicine-based approaches to target CSCs.

Highlights

The cell types transit in human body, which is identified by molecular profiles and contributes into the human disease (Regev et al, 2017)
The potential link between Epithelial-mesenchymal transition (EMT) and Cancer stem cell (CSC) is a key to cancer drug resistance acquisition, as well as cancer cell plasticity in which the cancer cells transform into the malignant cells and vice versa (Loret et al, 2019)
It has been reported that hypoxia-inducible factor (HIF)-1 promotes EMT of carcinoma cells in clear cell renal cell carcinoma, suppressing E-cadherin indirectly by inducing the expression of ZEB1 and ZEB2 and E2A immunoglobulin enhancer-binding factors E12/E47 (TCF3). Such inhibition leads to the mesenchymal characteristics to the carcinoma (Esteban et al, 2006; Krishnamachary et al, 2006). These findings indicate the complex contribution of various factors contributing to EMT in carcinoma cells, and represent a formidable challenge for formulating therapeutic approaches to control the EMT in tumors

Summary

Introduction

The cell types transit in human body, which is identified by molecular profiles and contributes into the human disease (Regev et al, 2017). The EMT and CSC pathways are regulated at gene level in several signaling pathways, where the plasticity is important for the cancer resistance. The cellular senescence can be targeted in terms of the acquisition of stemness of CSCs in cancer therapy (Del Barco et al, 2011; Olivos and Mayo, 2016).

Results

Conclusion