- Fibronectin is a large, extracellular matrix (ECM) glycoprotein that plays a central role in epithelial-to-mesenchymal transition (EMT) by facilitating cell-matrix interactions and promoting cell migration and invasion. During EMT, the expression of fibronectin is upregulated, which is crucial for the transition of epithelial cells to a more mesenchymal-like phenotype. This increase in fibronectin expression is associated with alterations in the ECM, enabling cells to detach from their original tissue structure and migrate through the extracellular matrix, a key feature of EMT.
- Fibronectin exists in both soluble and insoluble forms and participates in a wide range of cellular processes, including cell adhesion, migration, and differentiation. It interacts with integrins, such as α5β1, on the surface of mesenchymal cells, promoting cytoskeletal rearrangements that drive cell motility. This interaction also leads to the formation of focal adhesions, which are crucial for the cellular response to mechanical stress and ECM remodeling. In the context of EMT, the upregulation of fibronectin allows cells to integrate into the mesenchymal ECM and undergo morphological changes, including the formation of filopodia and lamellipodia, structures that aid in cell movement.
- The increased expression of fibronectin during EMT is regulated by several transcription factors, including Snail, Slug, Twist, and ZEB1, which are induced during the transition to a mesenchymal phenotype. These transcription factors help to repress epithelial genes and activate mesenchymal programs, including the upregulation of fibronectin. Additionally, growth factors such as TGF-β and Wnt signaling play a role in fibronectin induction during EMT by activating the Smad pathway and β-catenin signaling, respectively. These signaling pathways coordinate the remodeling of the ECM and promote the fibronectin-mediated adhesion and migration of mesenchymal cells.
- In pathological conditions such as cancer, fibrosis, and chronic inflammation, the upregulation of fibronectin is associated with increased cell migration, tissue remodeling, and fibrotic scarring. In cancer metastasis, for example, fibronectin’s role in ECM remodeling and its interaction with integrins contribute to the invasive behavior of tumor cells. In fibrotic diseases such as pulmonary fibrosis and liver cirrhosis, excessive fibronectin deposition in the ECM leads to the accumulation of scar tissue and impaired organ function. Similarly, in wound healing and inflammatory conditions, fibronectin plays a key role in tissue repair and remodeling, where its upregulation promotes cell migration and the formation of new tissue structures.
- Overall, fibronectin is not only a marker of EMT but also an essential functional component of the extracellular matrix that facilitates the morphological and behavioral changes associated with the epithelial-to-mesenchymal transition. By supporting cell adhesion, migration, and ECM remodeling, fibronectin plays a central role in both physiological processes like wound healing and pathological events such as cancer metastasis and fibrosis.
