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 |