Cell invasion plays crucial roles during normal development and in in many human diseases, especially in metastatic cancer. To date, the molecular mechanisms allowing cells to traverse through natural barriers like basement membranes (BM) remain poorly understood.
C. elegans is an excellent in vivo model to study cell invasion during normal development. During the L3 stage of hermaphrodite development, the specialized gonadal anchor cell (AC) breaches two BMs separating the gonad from the vulva precursor cells (VPCs). The AC then invades into the vulval epithelium to initiate vulval morphogenesis. Many genes regulating AC invasion as well as the structural components of the BM are highly conserved in C. elegans. Therefore AC invasion is a powerful model to study the first steps of tumor cell metastasis.
In order to identify novel regulators of anchor cell invasion, we performed a targeted RNAi screen and found that the components of the sumoylation pathway are important for AC invasion. By screening the genes encoding sumoylated proteins for a possible role during AC invasion, we identified icd-2 (inhibitor of cell death 2) and iff-2 (eukaryotic translation initiation factor 5A-2) as novel regulators of AC invasion. Both genes have orthologs in humans, contain classical and non-classical SUMO motifs and are essential for proper development. We are using a CRISPR/Cas9 approach to tag and further investigate the role of both of the identified proteins and sumoylation in cell invasion. Our results so far suggest that protein sumoylation is crucial for the AC invasion.