Engagement with the nucleus enhances the efficiency of basement membrane invasion

Abstract

Cell invasion through basement membrane (BM) extracellular matrix barriers is important during organ development, immune cell trafficking, and cancer metastasis. Here we study an invasion event, anchor cell (AC) invasion, which occurs during Caenorhabditis elegans development. The actin protrusion of the invading AC deforms then disrupts the BM. With live-cell imaging, we observe that the distal end of the actin protrusion contacts the nucleus during wild-type invasion, and deforms the nuclear envelope. Further we show that there is a correlation between invasion efficiency and nuclear contact: under mutant conditions where invasion is reduced, nuclear deformation is diminished. Knocking down the nuclear cytoskeleton protein lamin produces a nuclear positioning defect in the AC and reduces invasion efficiency. In keeping with this, both actin and microtubule-associated nesprins, ANC-1 and UNC-83 respectively, are found on the AC nuclear envelope during invasion, and perturbing their function reduces invasion. CEC-4, a chromodomain protein that attaches chromatin to the nuclear envelope in C. elegans, is also found to promote AC invasion. All together these data indicate that the positioning and properties of the AC nucleus are important for BM invasion. SUMMARY STATEMENTActin-based membrane protrusions in invading cells apply force to basement membrane (BM) barriers to help break through them. Here we provide evidence that the nucleus also plays a role in optimizing BM invasion.