The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion


Autoři: Ting Deng aff001;  Przemyslaw Stempor aff003;  Alex Appert aff003;  Michael Daube aff001;  Julie Ahringer aff003;  Alex Hajnal aff001;  Evelyn Lattmann aff001
Působiště autorů: Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse, Zürich, Switzerland aff001;  Molecular Life Science PhD Program, University and ETH Zurich, Zürich aff002;  The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge, United Kingdom aff003
Vyšlo v časopise: The Caenorhabditis elegans homolog of the Evi1 proto-oncogene, egl-43, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008470
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008470

Souhrn

Cell invasion allows cells to migrate across compartment boundaries formed by basement membranes. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells. Anchor cell (AC) invasion in C. elegans is an excellent in vivo model to study the regulation of cell invasion during development. Here, we have examined the function of egl-43, the homolog of the human Evi1 proto-oncogene (also called MECOM), in the invading AC. egl-43 plays a dual role in this process, firstly by imposing a G1 cell cycle arrest to prevent AC proliferation, and secondly, by activating pro-invasive gene expression. We have identified the AP-1 transcription factor fos-1 and the Notch homolog lin-12 as critical egl-43 targets. A positive feedback loop between fos-1 and egl-43 induces pro-invasive gene expression in the AC, while repression of lin-12 Notch expression by egl-43 ensures the G1 cell cycle arrest necessary for invasion. Reducing lin-12 levels in egl-43 depleted animals restored the G1 arrest, while hyperactivation of lin-12 signaling in the differentiated AC was sufficient to induce proliferation. Taken together, our data have identified egl-43 Evi1 as an important factor coordinating cell invasion with cell cycle arrest.

Klíčová slova:

Caenorhabditis elegans – Cell cycle and cell division – Gene expression – Gene regulation – Larvae – Notch signaling – RNA interference – Transcription factors


Zdroje

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Genetika Reprodukční medicína

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