Defective gap junctional intercellular communication in lung cancer: Loss of an important mediator of tissue homeostasis and phenotypic regulation

Gap junctions provide direct pathways for the exchange of molecules and ion s between neighboring cells, a process Known as gap junctional intercellula r communication (GJIC). This GJIC is important for homeostasis and regulati on of mitosis, differentiation, and apoptosis. Gal, junctions are present i n lung airway and alveolar epithelial cells and, in addition to the above r oles, might coordinate ciliary beating and surfactant secretion. GJIC is de creased in human and mouse lung carcinoma cells because of reduced expressi on of the gap junction protein, connexin43 (Cx43), and defects in signal tr ansduction pathways that mediate Cx43 function. This reduced GJIC is import ant in the behavior of lung carcinoma cells because forced expression of Cx 43 in lung carcinoma cells inhibits their growth and tumorigenicity. In thi s report, we summarize our studies on the role of GJIC in lung neoplasia.