Reference - Detail
| RRC ID | 45612 |
|---|---|
| Author | Matus DQ, Lohmer LL, Kelley LC, Schindler AJ, Kohrman AQ, Barkoulas M, Zhang W, Chi Q, Sherwood DR. |
| Title | Invasive Cell Fate Requires G1 Cell-Cycle Arrest and Histone Deacetylase-Mediated Changes in Gene Expression. |
| Journal | 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. |
| Volume | 35(2) |
| Pages | 162-74 |
| Published | 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 |
| Times Cited | 49 |
| WOS Category | DEVELOPMENTAL BIOLOGY CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 50 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm2217 |