RRC ID 45612
著者 Matus DQ, Lohmer LL, Kelley LC, Schindler AJ, Kohrman AQ, Barkoulas M, Zhang W, Chi Q, Sherwood DR.
タイトル Invasive Cell Fate Requires G1 Cell-Cycle Arrest and Histone Deacetylase-Mediated Changes in Gene Expression.
ジャーナル Dev Cell
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.
巻・号 35(2)
ページ 162-74
公開日 2015-10-26
DOI 10.1016/j.devcel.2015.10.002
PII S1534-5807(15)00629-2
PMID 26506306
PMC PMC4732529
MeSH Actins / genetics Actins / metabolism Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / biosynthesis* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Differentiation / genetics* Cyclin-Dependent Kinase Inhibitor Proteins / genetics Cyclin-Dependent Kinase Inhibitor Proteins / metabolism G1 Phase Cell Cycle Checkpoints / genetics* Gene Expression Regulation, Developmental Histone Deacetylases / biosynthesis* Histone Deacetylases / genetics Neoplasm Invasiveness / genetics* Neoplasm Invasiveness / pathology Podosomes / genetics Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / metabolism
IF 10.092
引用数 49
WOS 分野 DEVELOPMENTAL BIOLOGY CELL BIOLOGY
リソース情報
線虫 tm2217