Breaking theC. elegansinvasion/proliferation dichotomy

The acquisition of the post-mitotic state is crucial for the execution of many terminally differentiated cell behaviors during organismal development. However, the mechanisms that maintain the post-mitotic state in this context remain poorly understood. To gain insight into these mechanisms, we used the genetically and visually accessible model ofC. elegansanchor cell (AC) invasion into the vulval epithelium. The AC is a terminally differentiated uterine cell that must exit the cell cycle and enter a post-mitotic to initiate contact between the uterus and vulva through a cell invasion event. Here, we set out to identify the negative cell cycle regulators that maintain the AC in a post-mitotic, invasive state. Although our findings revealed a critical role for CKI-1 (p21CIP1/p27KIP1) in maintaining the post-mitotic state of the AC, loss of CKI-1 alone or in combination with other negative cell cycle regulators—including CKI-2 (p21CIP1/p27KIP1), LIN-35 (pRb/p107/p130), FZR-1 (Cdh1/Hct1), and LIN-23 (β-TrCP)—resulted in proliferating ACs that retained their invasive abilities. Upon examination of the gene regulatory network controlling AC invasion, we determined that proliferating, invasive ACs maintain pro-invasive gene expression. We therefore report that maintenance of the post-mitotic state is not necessary for AC invasion, breaking the previously establishedC. elegansinvasion/proliferation dichotomy.