De rol van DHHC20 bij de vorming van metastasen bij borstkanker

Metastasis is the primary reason for cancer-related deaths. Recent studies showed that palmitate enhances the metastatic ability of breast cancer cells. Previous data from the Fendt lab indicates that palmitate increases in the pre-metastatic niche and zDHHC20, a palmitoyl acyltransferase, could be important for palmitate-mediated lung metastasis formation. However, the underlying mechanism and the role of zDHHC20 in metastasizing cancer cells remain unclear. Thus, I hypothesize that disrupting palmitate metabolism and zDHHC20 mediated palmitoylation of certain substrates would reduce metastasizing cancer cells seeding in distant organs. Our goals of this project would be to address the following questions: 1) how does zDHHC20 mediated palmitoylation regulate metastasis formation; 2) the mechanism by which upstream regulators affect palmitoylation activity of zDHHC20 3) whether palmitate metabolism coupled with zDHHC20 mediated palmitoylation could be exploited as a therapeutic target in reducing metastasis formation. To achieve these goals, I will utilize palmitoylome, 13C tracer analysis, metabolomics, RNA sequencing, genetic manipulation, and pharmacologic interventions in vitro and in vivo. This project will shed some new light on the mechanistic knowledge of the interplay between nutrient and protein modification in breast cancer metastasis formation, which could provide insight into clinical intervention and treatment.