Insulation of cross-talk between signalingpathways-inspiration for innovative drug design / 中国药理学通报

Cross-talk of intracellular signaling pathways that share common components (hubs) is organized in form of a bow-tie network topology.Signaling cross-talk is functionally pleiotropic for target genes regulation, resulting in functional redundancy, synergism and antagonism, which should be precisely controlled to prevent signaling 'leaking' or 'spillover'.Thus, the biological system has evolved multiple insulating mechanisms to achieve stimulus-specific response that maintains intracellular homeostasis.The insulation mechanism of signaling cross-talk suggests: (1) the functional duality of cross-talk molecules that determine cell fate requires selectively targeting dysregulated cross-talk molecules while protecting the normal ones from off-target or unintended effects, and we propose them as the targetable cross-talk molecules;(2) cross-talk molecules are usually carried on the macromolecular complex as their functional platforms, thus the structural plasticity of conformational changes at the interaction surface of cross-talk molecules asks for intensive work on the relationship study between drug binding and biological activity, which we propose as the accessible cross-talk molecules.Therefore, signaling cross-talk and its insulation mechanism play instructive leading roles in resolving the bottlenecks of current drug R&D and improve the clinical outcome.

Specific Protein Markers for Stem Cell Cross-Talk with Neighboring Cells in the Environment

A stem cell interacts with the neighboring cells in its environment. To maintain a living organism's metabolism, either cell-cell or cell-environment interactions may be significant. Usually, these cells communicate with each other through biological signaling by interactive behaviors of primary proteins or complementary chemicals. The signaling intermediates offer the stem cell's functionality on its metabolism. With the rapid advent of omics technologies, various specific markers by which stem cells cooperate with their surroundings have been discovered and established. In this article, we review several stem cell markers used to communicate with either cancer or immune cells in the human body.