Invasive Cell Fate Requires G1 Cell-Cycle Arrest and Histone Deacetylase-Mediated Changes in Gene Expression.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Matus, DQ; Lohmer, LL; Kelley, LC; Schindler, AJ; Kohrman, AQ; Barkoulas, M; Zhang, W; Chi, Q; Sherwood, DR

Published Date

  • October 2015

Published In

Volume / Issue

  • 35 / 2

Start / End Page

  • 162 - 174

PubMed ID

  • 26506306

Pubmed Central ID

  • 26506306

Electronic International Standard Serial Number (EISSN)

  • 1878-1551

International Standard Serial Number (ISSN)

  • 1534-5807

Digital Object Identifier (DOI)

  • 10.1016/j.devcel.2015.10.002

Language

  • eng