title: LMO4 is an essential cofactor in the Snail2-mediated epithelial-to-mesenchymal transition of neuroblastoma and neural crest cells.
abstract: Neuroblastoma is an embryonic tumor derived from cells of the neural crest. Taking advantage of a newly developed neural crest lineage tracer and based on the hypothesis that the molecular mechanisms that mediate neural crest delamination are also likely to be involved in the spread of neuroblastoma, we were able to identify genes that are active both in neural crest development and neuroblastoma tumor formation. A subsequent search of the neuroblastoma gene server for human orthologues of genes differentially expressed in the chick embryo neural crest screen retrieved the LIM domain only protein 4 (LMO4), which was expressed in both cell types analyzed. Functional experiments in these two model systems revealed that LMO4 activity is required for neuroblastoma cell invasion and neural crest delamination. Moreover, we identified LMO4 as an essential cofactor in Snail2-mediated cadherin repression and in the epithelial-to-mesenchymal transition of both neural crest and neuroblastoma cells. Together, our results suggest that the association of high levels of LMO4 with aggressive neuroblastomas is dependent on LMO4 regulation of cadherin expression and hence, tumor invasiveness.
authors: Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas, Parc Científic de Barcelona, Barcelona 08028, Spain.
authors: Tiago
authors: T
authors: Ferronha
authors: M Angeles
authors: MA
authors: Rabadán
authors: Estel
authors: E
authors: Gil-Guiñon
authors: Gwenvael
authors: G
authors: Le Dréau
authors: Carmen
authors: C
authors: de Torres
authors: Elisa
authors: E
authors: Martí
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis / Q000502:physiology; D045744:Cell Line, Tumor; D002642:Chick Embryo; D004247:DNA / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics* / Q000502:physiology*; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D060588:LIM Domain Proteins / Q000235:genetics* / Q000502:physiology*; D016086:Lentivirus / Q000235:genetics; D008156:Luciferases / Q000502:physiology; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness / Q000235:genetics; D009432:Neural Crest / Q000473:pathology*; D009447:Neuroblastoma / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D013936:Thymidine / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D060588:LIM Domain Proteins; C114905:LMO4 protein, human; D034741:RNA, Small Interfering; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D004247:DNA; D008156:Luciferases; D013936:Thymidine