Molecular Mechanisms Regulating Epithelial Mesenchymal Transition (EMT) to Promote Cancer Progression
Saima Ghafoor, Elizabeth Garcia, Daniel J. Jay, Sujata Persad
Abstract
The process of epithelial-mesenchymal transition (EMT) is crucial in various physiological/pathological circumstances such as development, wound healing, stem cell behavior, and cancer progression. It involves the conversion of epithelial cells into a mesenchymal phenotype, which causes the cells to become highly motile. This reprogramming is initiated and controlled by various signaling pathways and governed by several key transcription factors, including Snail 1, Snail 2 (Slug), TWIST 1, TWIST2, ZEB1, ZEB2, PRRX1, GOOSECOID, E47, FOXC2, SOX4, SOX9, HAND1, and HAND2. The intracellular signaling pathways are activated/inactivated by signals received from the extracellular environment and the transcription factors are carefully regulated at the transcriptional, translational, and post-translational levels to maintain tight regulatory control of EMT. One of the most important pathways involved in this process is the transforming growth factor-β (TGFβ) family signaling pathway. This review will discuss the role of EMT in promoting epithelial cancer progression and the convergence/interplay of multiple signaling pathways and transcription factors that regulate this phenomenon.