Morphological and Functional Alterations of Occludens, Adherens, and Gap Junctions in Cancer

Abstract

Cell junctions are defined as structurally specialized domains that are formed at regions of contact between two cells, and to which both cells contribute an equal part. A number of different types of cell junctions, customarily subclassified on the basis of their ultrastructure, have been identified: adherens, occludens, and gap junctions (1,2). These junctions perform the following functions (1–4): (1) They provide strong intercellular adhesion and in turn are the basis for the formation of mechanically coherent tissues; (2) They mediate direct communication between cells by allowing the transfer of ions and small molecules from cell to cell without leakage into the extracellular compartment (metabolic coupling); (3) They act as intercellular conduits for electrochemical impulses (electrical coupling); and (4) They seal cells together into a coherent tissue that can act as a highly selective barrier to diffusion. In cancer, each type of intercellular junction can differ from its normal counterpart with respect to overall size, distribution at the cell surface, level of development, and numerical density (5). These differences may account for or contribute to some properties of malignant tumors, such as abnormalities in cell-to-cell adhesion, growth control, and transepithelial permeability. In this brief review, structural, biochemical, and functional features of the three major classes of cell junctions are summarized, emphasizing information that may be particularly pertinent to the cancer problem.

This work was supported by Public Health Service grant CA25034 from the National Cancer Institute and by funds from the Otho S.A. Sprague Memorial Institute.