The success of many metazoan developmental programs relies on the ability of specialized cells to transgress basement membranes (BMs). Cancer progression also relies on cellular invasion. Though the developmental and clinical importance of cell invasion is evident, studying its dynamics in vivo has proven to be challenging. Using high-resolution microscopy, as well as genetic and cell biological techniques we study the process of anchor cell (AC) invasion during C. elegans development. We have recently demonstrated that the conserved nuclear hormone receptor transcription factor, NHR-67, is required to maintain the AC in G1/G0 cell cycle arrest, a requirement for invasive behavior. Independent of cell cycle arrest, the AC utilizes the histone deacetylase, HDA-1, for the generation of invadopodia, and the expression of pro-invasive genes. These results suggest that invasion is a differentiated cellular behavior requiring cell cycle arrest and epigenetic modification of the genome. To identify additional chromatin modifiers that mediate invasion, we are conducting a tissue-specific RNAi screen. To date, we have identified several new pro-invasive genes which encode subunits of the SWI/SNF chromatin remodeling complex. The complex exhibits pleiotropy, and in C. elegans it contributes to cell fate specification in the somatic gonad, and cell-cycle exit and differentiation of muscle precursor cells. Here, we show a conserved role for the SWI/SNF complex in coordinating cell cycle arrest, as loss of
swsn-1 results in a mitotic AC. Specifically, we are examining the role of the SWI/SNF complex in maintenance of the post-mitotic state and the regulation of pro-invasive gene expression, through potential interactions with NHR-67, HDA-1, other chromatin modifiers and the cell cycle machinery. Together, these results will provide new insight into the role of the SWI/SNF complex in orchestrating invasive activity.