Is Epithelial-Mesenchymal Transition a New Roadway in the Pathogenesis of Oral Submucous Fibrosis: A Comprehensive Review

Epithelial-mesenchymal transition (EMT) collectively refers to a series of episodes that reshape polarized, intact epithelial cells into discrete motile cells that can conquer the extracellular matrix (ECM). It performs a pivotal role in embryonic development, wound healing, and tissue repair. Surprisingly, the exact mechanism can also lead to the onset of malignancy and organ fibrosis contributing to scar formation and loss of function. transforming growth factor signaling, WNT signaling, Notch signaling, Hedgehog signaling, and receptor tyrosine kinase signaling, as well as non-transcriptional changes in response to extracellular cues, such as growth factors and cytokines, hypoxia, and contact with the surrounding ECM, are responsible for the initiation of EMT. Although the pathogenesis of oral submucous fibrosis (OSMF) is multifactorial, compelling evidence suggests that it results from collagen deregulation. EMT is one of the spotlight events in the pathogenesis of OSMF, with myofibroblasts and keratinocytes being the victim cells. EMT is an essential step in both physiological and pathological events. The importance of EMT in the malignant development of OSMF and the inflammatory reaction preceding fibrosis implies a new upcoming area of research. This review aims to focus on the EMT events that function as a double-edged sword between wound healing and fibrosis and further discuss the mechanisms along with the molecular pathways that direct changes in gene expression essential for the same in the oral cavity. As OSMF involves a risk of malignant transformation, understanding the cellular and molecular events will open more avenues for therapeutic breakthroughs targeting EMT.