title: A non-cell-autonomous role for Ras signaling in C. elegans neuroblast delamination.
abstract: Receptor tyrosine kinase (RTK) signaling through Ras influences many aspects of normal cell behavior, including epithelial-to-mesenchymal transition, and aberrant signaling promotes both tumorigenesis and metastasis. Although many such effects are cell-autonomous, here we show a non-cell-autonomous role for RTK-Ras signaling in the delamination of a neuroblast from an epithelial organ. The C. elegans renal-like excretory organ is initially composed of three unicellular epithelial tubes, namely the canal, duct and G1 pore cells; however, the G1 cell later delaminates from the excretory system to become a neuroblast and is replaced by the G2 cell. G1 delamination and G2 intercalation involve cytoskeletal remodeling, interconversion of autocellular and intercellular junctions and migration over a luminal extracellular matrix, followed by G1 junction loss. LET-23/EGFR and SOS-1, an exchange factor for Ras, are required for G1 junction loss but not for initial cytoskeletal or junction remodeling. Surprisingly, expression of activated LET-60/Ras in the neighboring duct cell, but not in the G1 or G2 cells, is sufficient to rescue sos-1 delamination defects, revealing that Ras acts non-cell-autonomously to permit G1 delamination. We suggest that, similarly, oncogenic mutations in cells within a tumor might help create a microenvironment that is permissive for other cells to detach and ultimately metastasize.
authors.affiliation: Department of Genetics, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA Department of Biology, Georgian Court University, 900 Lakewood Avenue, Lakewood, NJ 08701, USA.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Parry
authors.affiliation: Department of Genetics, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA sundaram@mail.med.upenn.edu.
authors.forename: Meera V
authors.initials: MV
authors.lastname: Sundaram
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D060833:Cellular Microenvironment / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology*; D066246:ErbB Receptors / Q000378:metabolism; D007365:Intercellular Junctions / Q000502:physiology; D007668:Kidney / Q000166:cytology* / Q000196:embryology; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C066646:let-60 protein, C elegans; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C085873:let-23 protein, C elegans; D018631:ras Proteins
keywords: Caenorhabditis elegans; Delamination; EMT; Epithelia; Junction; Ras