Category: Assay Development and Screening
Cancer migration and invasion are two very important steps in the process of changing cells from locally growing primary tumor to life threating metastatic lesions. A lot of efforts has been put into investigating the mechanisms governing these two important milestones. However, cancer therapeutics that are designed according to our current understanding of these two steps have not proven to be effective in slowing down tumor progress in clinical trials. Here we use a high-throughput three-dimensional (3D) cell invasion platform along with a 2D migration assay system to identify the key epigenetic modulators and small molecules involved in invasion and migration using triple-negative, very invasive breast cancer cell line MDA-MB-231. The methods we used to find potential important players in these processes including alteration of epigenetic modulator’s expression using RNAi and small molecules screening in both traditional 2D migration system and more predictive 3D experimental system that mimic in vivo microenvironment more accurately. Epigenetic regulation via modifications such as DNA methylation, histone modification and chromatin remodeling affect a wide spectrum of gene targets involving in angiogenesis, tumor progression and survival. More and more studies approve that epigenetic regulation is a very important factor that control tumor cell invasion and migration. Screening the library of know epigenetic related genes, knocking down of which will decrease the metastatic ability of malignant breast cancer cells, could help us recognize more clinical –relevant targets. A parallel small molecule screening was also used to identify therapeutically desirable compounds that prevent cell invasion and migration. This study will lead to the development of new approaches for targeted treatments that have more clinical impact.
Jiaqi Fu– Research Fellow, NIH, Rockville, MD