A fundamental issue in cell biology is how the activation of a signaling pathway should lead to the appropriate cell response. Because of their oncogenic potential, the abundance, the duration and the localization of key signaling proteins must be carefully controlled. Negative feedback loops that combine transcription and protein-protein interactions are among the strategies by which a cell can turn off signaling. Our recent studies in Cancer Research and Autophagy show that degradation of key active proteins such as RHOA-GTP by constitutive autophagy represents one safeguard mechanism that limits signaling in a spatially and temporally restricted manner for faithful cytokinesis and directed migration. As a result, all autophagy compromises drive cytokinesis failure, aneuploidy, and motility-three processes that directly have an impact upon cancer progression. We therefore propose the term "signalphagy" to indicate a dedicated type of macroautophagy that degrades and thereby maintains the appropriate level of active signaling proteins to achieve tumor suppression.
Keywords: active RHOA; autophagy; cytokinesis; migration; signaling; tumor suppression.