Loss of genes that regulate uterine–vulva attachment in C. elegans results in two clear phenotypes: protruded vulva (Pvl) and egg-laying defective (Egl). Sherwood and colleagues used the 539 genes identified in previous RNA interference (RNAi) screens that induce these phenotypes to find 99 genes specifically involved in AC invasion through the basement membrane. Focusing on the genes that produced the most severe invasion defects after RNAi-mediated knockdown, they found that members of the cct chaperonin complex and six other genes — mep-1 (a zinc finger transcription factor), lit-1 (an orthologue of nemo-like kinase (
NLK
)), cdc-37, T03F1.8 (a guanylate kinase) and two uncharacterized genes (cacn-1 and T20B12.1) — were all upregulated in the AC before or during invasion. Vulval cells are known to induce AC invasion and the authors found that two genes, hbl-1 and unc-62 (orthologues of hunchback and homothorax, respectively), are required for vulval cell development and maturation ahead of AC invasion. Before invasion through the basement membrane occurs, netrin and integrin are known to establish an F-actin-rich invasive membrane in the AC. RNAi silencing of members of the cct complex, hda-1 (a histone deactylase) or mep-1 resulted in an absence of invasive membrane formation, and these genes seem to function independently of netrin and integrin.
These findings add to the evidence that invasion programmes that occur during development are relevant to metastasis
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