Epithelial-Mesenchymal Transition (EMT) and the Differences Between Epithelial and Mesenchymal Cells
Epithelial-Mesenchymal Transition (EMT) is a cellular process during which epithelial cells lose their epithelial characteristics and acquire mesenchymal features, resulting in increased migratory capacity and often invasive properties. 1
Definition and Significance of EMT
- EMT encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, leading to functional changes in cell migration and invasion 1
- EMT was first described in early embryogenesis studies as a program with well-defined cellular features 1
- EMT occurs in diverse physiological and pathological conditions including embryonic development, wound healing, cancer progression, and tissue fibrosis 1
- The reverse process, known as Mesenchymal-Epithelial Transition (MET), also occurs frequently during development 1
Key Characteristics of Epithelial Cells
- Epithelial cells are connected with each other via multiple types of junctions:
- Adherens junctions (connected to cortical actin bundles)
- Desmosomes (linked with cytokeratin intermediate filaments)
- Gap junctions
- Tight junctions (located at apical-lateral contact points) 1
- Exhibit distinct apical-basal polarity guided by polarity complexes (Par, Crumbs, and Scribble) 1
- Attached to underlying basement membrane via hemidesmosomes containing integrin 1
- Express epithelial markers such as E-cadherin and cytokeratins 1
- Form organized epithelial sheets with limited mobility 1
Key Characteristics of Mesenchymal Cells
- Lack functional epithelial junctions 1
- Display fibroblast-like morphology and cytoarchitecture 1
- Present back-front polarity in their actin stress fibers 1
- Contain vimentin-based intermediate filaments instead of cytokeratin-based ones 1
- Utilize integrin-containing focal adhesions to attach to extracellular matrix 1
- Exhibit increased migratory capacity and often invasive properties 1
- Express mesenchymal markers such as vimentin and N-cadherin 2
EMT Spectrum and Plasticity
- EMT is not a binary switch but rather a spectrum of states between fully epithelial and fully mesenchymal phenotypes 1
- Cells can exist in intermediate states with both epithelial and mesenchymal characteristics 1
- This plasticity has been referred to as partial EMT, hybrid E/M status, metastable EMT state, EMT continuum, or EMT spectrum 1
- Epithelial-Mesenchymal Plasticity (EMP) indicates the ability to move between various states along this spectrum 1
- The intermediate states can be diverse depending on biological context 1
Molecular Regulation of EMT
- EMT is driven by EMT-associated transcription factors (EMT-TFs) including:
- These transcription factors repress epithelial genes, particularly E-cadherin, by binding to E-boxes in their promoters 2
- Post-transcriptional and post-translational regulation of EMT regulators is crucial in controlling EMT 1
- Multiple signaling pathways regulate EMT including:
Clinical Significance of EMT
- EMT plays a critical role in cancer progression and metastasis 5, 6
- Cancer cells undergoing EMT may acquire stem-like features and resistance to chemotherapy 5
- EMT contributes to tissue fibrosis in various organs 1
- Understanding EMT mechanisms has implications for developing targeted therapies against cancer metastasis 2
Important Considerations When Studying EMT
- EMT status cannot be assessed based on one or a small number of molecular markers 1
- The primary criteria for defining EMT should include changes in cellular properties together with a set of molecular markers 1
- Post-transcriptional regulation at both mRNA and protein levels is crucial but often neglected in studies that use RNA expression exclusively 1
- EMT-TFs are also expressed in non-epithelial cells and can play roles beyond classic EMT phases 1