The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion.
PLoS Genet
; 16(3): e1008470, 2020 03.
Article
en En
| MEDLINE
| ID: mdl-32203506
ABSTRACT
Cell invasion allows cells to migrate across compartment boundaries formed by basement membranes. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells. Anchor cell (AC) invasion in C. elegans is an excellent in vivo model to study the regulation of cell invasion during development. Here, we have examined the function of egl-43, the homolog of the human Evi1 proto-oncogene (also called MECOM), in the invading AC. egl-43 plays a dual role in this process, firstly by imposing a G1 cell cycle arrest to prevent AC proliferation, and secondly, by activating pro-invasive gene expression. We have identified the AP-1 transcription factor fos-1 and the Notch homolog lin-12 as critical egl-43 targets. A positive feedback loop between fos-1 and egl-43 induces pro-invasive gene expression in the AC, while repression of lin-12 Notch expression by egl-43 ensures the G1 cell cycle arrest necessary for invasion. Reducing lin-12 levels in egl-43 depleted animals restored the G1 arrest, while hyperactivation of lin-12 signaling in the differentiated AC was sufficient to induce proliferation. Taken together, our data have identified egl-43 Evi1 as an important factor coordinating cell invasion with cell cycle arrest.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proto-Oncogenes
/
Expresión Génica
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
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Puntos de Control del Ciclo Celular
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Puntos de Control de la Fase G1 del Ciclo Celular
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Proteína del Locus del Complejo MDS1 y EV11
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Suiza