Some abstracts do not have video files because ASAS was denied recording rights.
191
Signaling endosomes and epithelial morphogenesis
Tumor development in glandular tissues is associated with structural alterations in the hollow ducts and spherical structures that comprise such tissues. We have described a signaling axis that provokes dramatic changes in the organization of epithelial cysts, reminiscent of tumorigenic glandular phenotypes. In reconstituted basement membrane cultures of renal epithelial cysts, enhanced activation ARF6 (ADP-ribosylation factor 6) downstream of receptor tyrosine kinases induces the formation of cell-filled glandular structures with aberrant phenotypes. All of these alterations are accompanied by growth factor receptor internalization into signaling endosomes and reversed by blocking ARF6 activation or receptor endocytosis. Receptor localization in signaling endosomes results in hyperactive extracellular signal-regulated kinase signaling leading to abnormal cellular alterations. These findings identify a link between ARF6-regulated receptor internalization and events that drive dramatic alterations in epithelial glandular morphogenesis providing new mechanistic insight into the molecular processes that can promote epithelial glandular disruption.
Keywords: ARF6, epithelial morphogenesis, signaling endosomes