Clinical Implications of EMT in HNSCC: A Review of the Factors and Pathways at Play

Abstract

_Background: _Epithelial–mesenchymal transition (EMT) is effected in squamous cell cancers via activation of the cadherin switch. Activation of the switch results in decreased expression of E-cadherin and increased expression of N-cadherin. This results in loss of cell-cell adhesion and cellular polarity and allows the tumour cells to metastasise. _Aims_ _&_ _Objectives:_ This systematic review was carried out to find the clinical implications of EMT in HNSCC and bring together the molecular, genetic, and epigenetic pathways found to be acting on the cadherin switch. _Materials & Methods: _An extensive search for relevant papers was made on PubMed, Medline, and Google Search. Only good-quality studies pertaining to epithelial–mesenchymal transition in oral cavity cancers in humans were selected. Furthermore, all selected papers were assessed for their clinical relevance. _Results: _The cadherin switch is regulated by transcription factors like Snail, SLUG, ZEB1, and ZEB2. It is also acted on by epigenetic modifiers. These transcription factors are regulated by multiple pathways like Wnt/β–catenin, PI3K/AKT, MAPK, etc. These pathways are in turn regulated by molecular and external agents like NNK from tobacco smoke, hypoxia, the DDB2 gene, reactive oxygen species (ROS), and melatonin.