The Tumor suppressing protein P53, already known as the guardian of the genome for its cancer-fighting action by which it blocks cell division in case of malignancy, is now also getting attention for its role in tissue repair in a study by molecular biologists from the universities of Bristol and Cambridge. This work which is published in the journal Science, provides a new understanding of the molecular mechanisms and factors involved in epithelialization and wound healing, but more generally in cell migration – and thus the spread of cancer.
The research identifies a new key role for p53 in epithelial migration and tissue repair. It provides a new understanding of the processes that cells use during the tissue repair process, opening up new avenues for improving wound healing.
Epithelial tissue forms the lining that protects the outer skin and internal cavities of the body, and its inherent ability to self-repair is great. We already know that the wounded epithelium is known to repair itself because of the ability of the remaining cells to migrate collectively to seal the “hole” and close the wound edges together and seal them.
Leader cells play an important role
Leader cells originate from the damaged epithelial cells and promote epithelial migration and epithelialization. However, the molecules and signals that give certain epithelial cells this leader function are still not known.
The research decoded the molecular program that turns these cells into migratory leader cells so that the wound can be closed quickly. The same molecular program also ensures that these highly migratory cells are removed once the wound is healed, allowing the tissue to return to a normal epithelial structure. Using a simplified model of epithelial sheets scraped in vitro to damage the epithelial monolayer, the researchers were able to identify the molecular signal that causes the leader cells to emerge.
One molecular signal designates the leader cells: after injury, cells at the edge of the epithelial space increase the level of p53 and p21 proteins, triggering the cell migration program. Once epithelialization is complete, the leader cells are eliminated by their healthy epithelial neighbors. The injured cells may have participated in wound closure, but are then sacrificed to preserve functional epithelial tissue with normal morphology.
The 2 main roles of p53
The small protein plays 2 important roles in epithelial repair. It triggers the epithelial program of epithelial closure, and once the repair is complete, it induces the removal of the leader cells.
Lead author Dr. Giulia Pilia, a researcher at the University of Bristol, comments on the findings, “Collective migration is important in many other areas, such as cancer, where groups of cells move together from the primary tumor to form metastases. It would be important to know whether the same proteins identified in the wounds are involved in these other contexts.”