A New Tumor Suppressor That Regulates Tissue Architecture

Pathologists use loss of normal tissue architecture as a key criterion to identify and categorize disease states. Epithelia in all glandular structures in vivo have a characteristic organization where they line a central lumen and are involved in absorptive and/or secretory functions. Under some physiological conditions— such as pregnancy, wound healing, and the periodic tissue remodeling that occurs in tissues such as colon—there is a significant increase in the rate of cell proliferation. Although the proliferation rate in these physiological conditions is higher than that seen under disease states, the overall tissue size and structure are maintained. Such maintenance of size/ structure occurs because the increased proliferation is tightly coupled with tissue morphogenesis programs, resulting in remodeling of normal tissue architecture. Aberrant expression of drivers of proliferation, such as growth factors, can induce untimely proliferation of epithelia that results in hyperplastic overgrowth of ducts and alveoli. Despite the increase in cell number, such overgrowth by itself is usually not a cause for concern. However, when the increase in cell number is coupled with atypical changes in tissue architecture—such as changes in the organization of epithelia around a lumen, multilayering of the epithelial lining in glandular structures, and changes in cell size or shape—this is usually a cause for concern. While pathways that regulate cell proliferation have been intensely investigated over the past decades, the pathways that regulate cell architecture and tissue organization are poorly understood.