Cell–cell communication: new insights and clinical implications

AbstractMulticellular organisms are composed of diverse cell types that must coordinate their behaviors through communication. Cell–cell communication (CCC) is essential for growth, development, differentiation, tissue and organ formation, maintenance, and physiological regulation. Cells communicate through direct contact or at a distance using ligand–receptor interactions. So cellular communication encompasses two essential processes: cell signal conduction for generation and intercellular transmission of signals, and cell signal transduction for reception and procession of signals. Deciphering intercellular communication networks is critical for understanding cell differentiation, development, and metabolism. First, we comprehensively review the historical milestones in CCC studies, followed by a detailed description of the mechanisms of signal molecule transmission and the importance of the main signaling pathways they mediate in maintaining biological functions. Then we systematically introduce a series of human diseases caused by abnormalities in cell communication and their progress in clinical applications. Finally, we summarize various methods for monitoring cell interactions, including cell imaging, proximity-based chemical labeling, mechanical force analysis, downstream analysis strategies, and single-cell technologies. These methods aim to illustrate how biological functions depend on these interactions and the complexity of their regulatory signaling pathways to regulate crucial physiological processes, including tissue homeostasis, cell development, and immune responses in diseases. In addition, this review enhances our understanding of the biological processes that occur after cell–cell binding, highlighting its application in discovering new therapeutic targets and biomarkers related to precision medicine. This collective understanding provides a foundation for developing new targeted drugs and personalized treatments.