Targeting GPR110 in HER2-Overexpressing Breast Cancers
Technical Report,30 Sep 2014,29 Sep 2015
Baylor College Of Medicine Houston United States
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Identification of drug targets with novel mechanism of actions as well as excellent safety profile is needed to improve thechemotherapy-sparring regimen of anti-HER2 drug combination lapatinib L trastuzumab T LT, which is effective in a larger group of patients. Drugs targeting G protein-coupled receptors GPCRs have low toxicity because of their high specificity and target-selectivity. In a GPCR expression profiling study and subsequent in vitro studies, we have identifiedGPR110 as a potential candidate in HER2 breast cancer. Our overall goals of the proposed research are to investigate the role of GPR110 in tumorigenicity and anti-HER2 drug resistance in HER2 BC. In the first year of the funded study, we have shown that GPR110 overexpression occurs commonly in various anti-HER2 drug resistant cells and in tumorigenic population using a broad panel of cell line models. We have successfully generated inducible lentiviral plasmids with GPR110 cDNA and cell lines that inducibly overexpress GPR110. Generation of cell lines with lentiviral plasmids containing GPR110 shRNA is ongoing. Using GPR110-overexpression and siRNA-mediated knockdown strategies, we have also demonstrated thatGPR110 may contribute to tumorigenicity in HER2 breast cancer. Further, we have uncovered previously unanticipated role of GPR110 in cell adhesion, invasion, and migration, which may facilitate anti-HER2 drug resistance. In vitro and in vivo experiments proposed in the coming years will further establish a role of GPR110 in HER2 breast cancer.