Abstract IA05: Regulation of Ras proteins and their effectors

Ras proteins regulate multiple phenotypes, including proliferation, contact inhibition, cell motility, metabolism, and genome integrity. This range of phenotypes may relate to the number of different effector pathways that Ras activates. The best validated of these is the Raf/MAPK pathway. Ras proteins can activate PI 3-kinase pathways directly, though this seems to vary between tissue types. Ras proteins bind and activate RalGDS, but this pathway is less well understood. In addition to these three major pathways, Ras proteins in their GTP state interact directly with several other potential effectors.Analysis of the contributions that these pathways make towards cancer phenotypes using genetic approaches or RNA interference has been complicated by redundancies within each effector pathway. For example, there are three Raf isoforms, 3 PI 3-kinase isoforms, etc. This explains why screens for single genes that Ras depends on have not identified classical Ras effectors. Furthermore, each pathway may have several relevant phenotypes, such as effects on cell cycle progression, survival, and metabolic stress. Therefore, screens that depend on one phenotype, such as proliferation or survival, might miss other important functions. In addition to these technical complications, it is important to recognize differences in signaling between different tumor types. For example, in lung adenocarcinoma, the RTK/RAS/MAPK pathway can be activated by mutations in RTKs, activation of SOS, loss o...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Oncogenic Signals Translate the Cancer Genome Source Type: research