positive regulation of epithelial to mesenchymal transition

Definition

Target type: biologicalprocess

Any process that increases the rate, frequency, or extent of epithelial to mesenchymal transition. Epithelial to mesenchymal transition is where an epithelial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell. [GOC:BHF, GOC:dph, GOC:tb]

Positive regulation of epithelial to mesenchymal transition (EMT) is a complex biological process that involves a coordinated switch in cellular phenotype from an epithelial state, characterized by cell-cell junctions and polarity, to a mesenchymal state, characterized by migratory and invasive capabilities. This transition is crucial during development, wound healing, and cancer metastasis. The process is tightly regulated by a network of signaling pathways, transcription factors, and epigenetic modifications.

**Key Regulatory Events:**

- **Loss of cell-cell adhesion:** Epithelial cells are held together by tight junctions and adherens junctions. During EMT, these junctions are disassembled, allowing cells to detach from their neighbors. This process is often mediated by the downregulation of cell adhesion molecules like E-cadherin and the upregulation of mesenchymal markers like N-cadherin.

- **Gain of motility and invasiveness:** EMT promotes cell motility and invasiveness by activating signaling pathways that promote cytoskeletal reorganization, matrix metalloproteinase (MMP) expression, and cell migration. Key signaling pathways involved include the TGF-β pathway, Wnt pathway, and Hedgehog pathway.

- **Changes in cell morphology:** Epithelial cells are typically cuboidal or columnar in shape, while mesenchymal cells are more elongated and fibroblast-like. This morphological shift is driven by changes in cytoskeletal organization and the expression of specific cytoskeletal proteins.

- **Epigenetic modifications:** DNA methylation and histone modifications play a role in regulating gene expression during EMT. These modifications can influence the expression of key transcription factors and signaling molecules involved in the transition.

**Molecular Players:**

- **Transcription factors:** EMT is regulated by a variety of transcription factors, including Snail, Slug, Twist, and Zeb1/2. These factors can repress the expression of epithelial genes and activate the expression of mesenchymal genes.

- **Signaling molecules:** Several signaling pathways are involved in EMT, including:
- **TGF-β pathway:** Activates downstream targets like Smad proteins, which regulate the expression of EMT-inducing genes.
- **Wnt pathway:** Influences cell fate decisions and promotes mesenchymal differentiation.
- **Hedgehog pathway:** Promotes cell proliferation, survival, and motility.

**Clinical Significance:**

EMT is a critical process in the development and progression of various cancers. Tumor cells undergoing EMT gain invasive properties, enabling them to spread to distant sites and form metastases. Understanding the mechanisms underlying EMT is crucial for developing novel therapeutic strategies to target cancer metastasis.

**Note:** The process of positive regulation of EMT involves the activation or upregulation of the molecular players described above. This can be achieved through various mechanisms, including signaling pathway activation, transcription factor binding, and epigenetic modifications.'
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Proteins (16)

Compounds (491)