PT  - JOURNAL ARTICLE
AU  - Ting Deng
AU  - Michael Daube
AU  - Alex Hajnal
AU  - Evelyn Lattmann
TI  - The &lt;em&gt;C. elegans&lt;/em&gt; homolog of the &lt;em&gt;Evi1&lt;/em&gt; proto-oncogene, &lt;em&gt;egl-43&lt;/em&gt;, coordinates G1 cell cycle arrest with pro-invasive gene expression during anchor cell invasion
AID  - 10.1101/802355
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 802355
4099  - http://biorxiv.org/content/early/2019/10/11/802355.short
4100  - http://biorxiv.org/content/early/2019/10/11/802355.full
AB  - 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 a critical factor coordinating cell invasion with cell cycle arrest.Author summary Cells invasion is a fundamental biological process that allows cells to cross compartment boundaries and migrate to new locations. Aberrant cell invasion is a first step during the formation of metastases by malignant cancer cells.We have investigated how a specialized cell in the Nematode C. elegans, the so-called anchor cell, can invade into an adjacent epithelium. Our work has identified an oncogenic transcription factor that controls the expression of specific target genes necessary for cell invasion, and at the same time inhibits the proliferation of the invading anchor cell.These findings shed light on the mechanisms, by which cells decide whether to proliferate or invade.