Author: Matus, David Q.; Lohmer, Lauren L.; Kelley, Laura C.; Schindler, Adam J.; Kohrman, Abraham Q.; Barkoulas, Michalis; Zhang, Wan; Chi, Qiuyi; Sherwood, David R.
Description: 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.
Subject headings: Actins; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cell Differentiation; Cyclin-Dependent Kinase Inhibitor Proteins; G1 Phase Cell Cycle Checkpoints; Gene Expression Regulation, Developmental; Histone Deacetylases; Neoplasm Invasiveness; Podosomes; Receptors, Cytoplasmic and Nuclear; C elegans
Publication year: 2015
Journal or book title: Developmental Cell
Volume: 35
Issue: 2
Pages: 162-174
Find the full text: https://www.strategian.com/fulltext/Matus2015.pdf
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Serial number: 3758