Cell extrusion

Cell extrusion is a vital cellular process that plays a crucial role in maintaining the integrity and homeostasis of epithelial tissues. This process involves the removal of live or dead cells from an epithelium without disrupting the epithelial barrier. Cell extrusion can occur in two main forms: apoptotic cell extrusion, where cells destined to die are removed, and compensatory cell extrusion, where living cells are expelled to maintain tissue density after cell division.

Mechanisms of Cell Extrusion

Cell extrusion is a highly regulated process that involves several key mechanisms and signaling pathways. The most well-understood mechanism is the Sphingosine-1-phosphate (S1P) pathway, which is crucial for apoptotic cell extrusion. In this pathway, the dying cell produces S1P, a signaling lipid, which acts on neighboring cells to contract and form a ring that pushes the dying cell out of the epithelium.

Compensatory cell extrusion is less understood but is thought to involve changes in cell adhesion and the actomyosin cytoskeleton. This form of extrusion ensures tissue integrity is maintained after cell division by balancing cell numbers.

Roles and Importance

Cell extrusion serves several important functions in epithelial tissues:

• Maintaining Tissue Homeostasis: By removing dying or excess cells, cell extrusion helps maintain the correct cell density and tissue architecture.
• Barrier Function: It ensures the epithelial barrier is not compromised during cell removal, which is crucial for protecting against pathogens and maintaining tissue function.
• Tissue Repair and Regeneration: Cell extrusion is involved in the removal of damaged cells, allowing for the repair and regeneration of tissues.
• Cancer: Abnormalities in cell extrusion can contribute to cancer progression by allowing the survival of potentially malignant cells or by disrupting tissue architecture.

Regulation of Cell Extrusion

The regulation of cell extrusion involves several factors, including cellular signals, mechanical forces, and the extracellular matrix. Changes in the expression or activity of molecules involved in cell adhesion (e.g., E-cadherin), cell signaling (e.g., Sphingosine-1-phosphate receptor), and cytoskeletal dynamics can influence cell extrusion rates and patterns.

Clinical Implications

Understanding the mechanisms and regulation of cell extrusion has significant clinical implications. For example, targeting the pathways involved in cell extrusion could offer new strategies for cancer therapy by promoting the removal of cancerous cells. Additionally, enhancing cell extrusion may aid in tissue repair and regeneration following injury.

Research Directions

Future research in the field of cell extrusion is likely to focus on uncovering the molecular details of compensatory cell extrusion, exploring the role of cell extrusion in disease contexts beyond cancer, and developing therapeutic strategies that manipulate cell extrusion for tissue engineering and regenerative medicine.