Bringing balance by force: Live cell extrusion controls epithelial cell numbers

To function as an intact barrier, epithelia must maintain constant cell numbers despite high rates of turnover. If the rate of death exceeds proliferation, epithelial barrier function could become compromised; if it lags behind proliferation, cells could amass into tumors. Although the balance between cell death and division is critical for preventing pathology,most studies focus on each process in isolation. Loss of contact inhibition is a hallmark of cancer cells and has suggested that cell contacts are important for linking rates of cell division and death. However, epithelial cells continuously divide and die while maintaining contacts with each other, so other factors must control this balance. Recent studies have found that cell-crowding forces from cell proliferation can drive cells to die by extrusion from the epithelium. Factors thatalter thisresponsetocellcrowding mayleadtobarrier function diseases or promote hyperplasia and cancer.