Abstract

Epithelial-to-mesenchymal transition (EMT) is a fundamental cellular phenomenon that plays an intrinsic role in development, tissue repair, and cancer progression. EMT is tightly regulated by transcription factors that alter gene expression to promote epithelial to mesenchymal phenotype. EMT is also regulated by a diverse array of cytokines and growth factors whose activities are deregulated during malignancy. EMT enables tumor cells to exist in various intermediate states along the epithelial-mesenchymal phenotypic axis that transit from cancer stem cells (CSCs) to circulating tumor cells (CTCs). Recent studies have revealed the importance of CSCs in tumor promotion, invasion and metastasis. The relapsed tumors encompass CSCs which are resistant to radiotherapy and chemotherapy. In this review, we have summarized our current understanding of the molecular mechanisms that regulate EMT induced CSC phenotype. We have highlighted studies implicating the function of TGF-�, Wnt, and Notch regulated non-coding RNAs in driving EMT promoting CSC self-renewal. Finally, we discuss how the EMT and CSCs cause drug resistance with the hope to overcome such resistance as a possible approach for cancer treatment.

Highlights

  • Epithelial-mesenchymal transition is a cellular phenomenon that allows a stationary polarized epithelial cell to undergo various morphological changes to assume a migratory, invasive mesenchymal cell phenotype

  • Cancer metastasis is driven by epithelial to mesenchymal transition (EMT) mainly by conversion of cancer cells to cancer stem cells (CSCs), which are capable of traversing tissue boundaries, entering into the blood vessels, localizing and growing in other tissues to form metastatic foci

  • We focus on EMT, plasticity, circulating tumor cells (CTCs), cancer stemness with an emphasis on the the role of cellular signaling in development of EMT in head and neck squamous cell carcinoma (HNSCC) and breast cancers (BC)

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Summary

INTRODUCTION

Epithelial-mesenchymal transition is a cellular phenomenon that allows a stationary polarized epithelial cell to undergo various morphological changes to assume a migratory, invasive mesenchymal cell phenotype. The process known as epithelial to mesenchymal transition (EMT) is an intrinsic cellular phenomenon reminiscent of embryonic development and tissue repair, which occurs during diverse disease processes including cancer invasion, organ fibrosis [2]. The activation of EMT-TFs occurs in response to various signaling pathways such as Transforming Growth Factor β (TGF-β), Wnt and Notch. These extracellular signals activate the intracellular kinase cascades which induce the expression of EMT-TFs. EMT and mesenchymal to epithelial transition (MET) which involves the conversion of mesenchymal cells to epithelial cells are consistent with the idea of cell plasticity. We focus on EMT, plasticity, CTCs, cancer stemness with an emphasis on the the role of cellular signaling in development of EMT in head and neck squamous cell carcinoma (HNSCC) and breast cancers (BC)

EPITHELIAL-MESENCHYMAL TRANSITION
EMT in development
Transcriptional regulation of EMT
EMT and CTCs in cancer: A starting point for invasion and metastasis
EMT AND CANCER STEMNESS
Overview of cancer stem cells
Plasticity and reversibility of normal and CSC
EMT and CSCs
REGULATION OF EMT BY CELL SIGNALING
Wnt Signaling and EMT
TGF-β Signaling and EMT
Notch Signaling and EMT
CURRENT STATUS AND THERAPEUTIC POTENTIAL
PERSPECTIVES
E D Hay
13. J A Davies
16. A Desmouliere
Findings
94. D Meulemans and M Bronner-Fraser
Full Text
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