Epidermal growth factor and trail interactions in epithelial-derived cells.
In healthy tissues, there is a balance between cell survival and death. This balance ensures epithelial cells survive in the right milieu, but undergo programmed cell death (apoptosis) when the environment is no longer supportive. Cells sense these changes primarily through receptors on the cell surface that bind to specific ligands present in the extracellular environment. These receptors, through signal transduction pathways, lead to promotion of cell survival or induction of cell death. One of the most important types of receptors regulating cell survival is the epidermal growth factor (EGF) receptors, while one of the most important types of receptors regulating apoptosis is the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors. EGF receptors activate survival signaling pathways including PI3K/AKT, Ras/MAPK, and JAK/STAT signaling pathways leading to cell survival. TRAIL activates apoptotic signaling pathways leading to caspase activation and mitochondrial dysfunction. The balance between these two signaling pathways determine whether a cell survives or dies. In disease states, this balance is altered. For example, epithelial-derived cancer cells often have increased expression of EGF receptors and are resistant to apoptosis. Understanding the interactions between survival and apoptotic signaling pathways mediated by EGF receptors and TRAIL death receptors will be essential to explain the role these pathways play in healthy and diseased cells.
Gibson
Spencer Bruce
SB
Department of Biochemistry and Medical Genetics Manitoba Institute of Cell Biology, University of Manitoba Winnipeg, Manitoba R3E 0V9, Canada.
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002470:Cell Survival; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000502:physiology*; D004847:Epithelial Cells; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors