RESUMO
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.
RESUMO
G protein-coupled receptors (GPCRs) are the largest cell surface receptor family, which mediates activities of almost all known cellular response to ligands, including hormones release, neurotransmitters and sensory input.GPCRs can promote development and progression of gastric cancer, colorectal cancer, lung cancer and breast cancer and other tumors.Tyrosine kinase receptors (RTKs) are another important family of membrane receptors, which can regulate cell proliferation, differentiation, migration and survival.Overexpression of RTKs has been found in many cancer cells.Therefore, GPCRs and RTKs are equally important in the clinical treatment of cancer therapeutic.However, GPCRs and RTKs are not independent, and they can use common signal transduction.The present study show that crosstalk between GPCRs and RTKs can facilitate migration of lung epithelial cells, increasing survival of nerve cells and promoting tumor occurrence and development.This article mainly focuses on crosstalk between GPCRs and RTKs and their roles in tumorigenesis and oncotherapy.
RESUMO
JAK/STAT is a pleiotropic signal transduction pathway with functions of regulating proliferation, differentiation and apoptosis in the cell. Recent research has shown that it plays an important role in embryonic development, brain tumors, cerebral ischemia and neural stem cell(NSC) proliferation process after brain injuries. Notch signaling pathway exists in all known animal cells, and it is a classic signaling pathway in the regulation of NSC proliferation and differentiation. Under the guidance of the network pharmacology, this article casts light on the crosstalk between JAK/STAT and Notch signal pathway in NSC proliferation, with the aim to provide basic theoretical supports in the research of drugs with the effectiveness of neuroprotection and NSC regulation after cerebral ischemia.
RESUMO
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.