Invasive Cell Fate Requires G1 Cell-Cycle Arrest and Histone Deacetylase-Mediated Changes in Gene Expression.
Dev Cell
; 35(2): 162-74, 2015 Oct 26.
Article
em En
| MEDLINE
| ID: mdl-26506306
ABSTRACT
Despite critical roles in development and cancer, the mechanisms that specify invasive cellular behavior are poorly understood. Through a screen of transcription factors in Caenorhabditis elegans, we identified G1 cell-cycle arrest as a precisely regulated requirement of the anchor cell (AC) invasion program. We show that the nuclear receptor nhr-67/tlx directs the AC into G1 arrest in part through regulation of the cyclin-dependent kinase inhibitor cki-1. Loss of nhr-67 resulted in non-invasive, mitotic ACs that failed to express matrix metalloproteinases or actin regulators and lack invadopodia, F-actin-rich membrane protrusions that facilitate invasion. We further show that G1 arrest is necessary for the histone deacetylase HDA-1, a key regulator of differentiation, to promote pro-invasive gene expression and invadopodia formation. Together, these results suggest that invasive cell fate requires G1 arrest and that strategies targeting both G1-arrested and actively cycling cells may be needed to halt metastatic cancer.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Proteínas de Caenorhabditis elegans
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Pontos de Checagem da Fase G1 do Ciclo Celular
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Histona Desacetilases
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Invasividade Neoplásica
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article