RRC ID 47662
Author Vaughen J, Igaki T.
Title Slit-Robo Repulsive Signaling Extrudes Tumorigenic Cells from Epithelia.
Journal Dev Cell
Abstract Cells dynamically interact throughout animal development to coordinate growth and deter disease. For example, cell-cell competition weeds out aberrant cells to enforce homeostasis. In Drosophila, tumorigenic cells mutant for the cell polarity gene scribble (scrib) are actively eliminated from epithelia when surrounded by wild-type cells. While scrib cell elimination depends critically on JNK signaling, JNK-dependent cell death cannot sufficiently explain scrib cell extirpation. Thus, how JNK executed cell elimination remained elusive. Here, we show that repulsive Slit-Robo2-Ena signaling exerts an extrusive force downstream of JNK to eliminate scrib cells from epithelia by disrupting E-cadherin. While loss of Slit-Robo2-Ena in scrib cells potentiates scrib tumor formation within the epithelium, Robo2-Ena hyperactivation surprisingly triggers luminal scrib tumor growth following excess extrusion. This extrusive signaling is amplified by a positive feedback loop between Slit-Robo2-Ena and JNK. Our observations provide a potential causal mechanism for Slit-Robo dysregulation in numerous human cancers.
Volume 39(6)
Pages 683-695
Published 2016-12-19
DOI 10.1016/j.devcel.2016.11.015
PII S1534-5807(16)30827-9
PMID 27997825
PMC PMC6207184
MeSH Animals Cadherins / metabolism Carcinogenesis / metabolism Carcinogenesis / pathology Clone Cells Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism* Epithelium / metabolism* Epithelium / pathology* Feedback, Physiological JNK Mitogen-Activated Protein Kinases / metabolism Models, Biological Neoplasms / metabolism* Neoplasms / pathology* Nerve Tissue Proteins / metabolism* Receptors, Immunologic / metabolism* Signal Transduction* Up-Regulation
IF 10.092
Times Cited 37