LMO4 is an Essential Cofactor in the Snail2-Mediated Epithelial-to-Mesenchymal Transition of Neuroblastoma and Neural Crest Cells
Por:
Ferronha T, Rabadán MA, Gil-Guiñon E, Le Dréau G, de Torres C and Martí E
Publicada:
13 feb 2013
Categoría:
Neuroscience (miscellaneous)
Resumen:
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.
hybrid, Green Published
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