A Kras Driven Murine Model Elucidates Oncogenic Role of FADD in lung cancer

Lung adenocarcinoma is the most common type of non-small cell lung cancer, causing more than 500,000 deaths per year worldwide [5]. This research aims to investigate the role of Fasassociated protein with death domain (FADD) in lung adenocarcinomas in hopes of identifying a clinical biomarker and/or therapeutic target for the disease. Recent studies in lung cancer have indicated a correlation between phosphorylated FADD (p-FADD), induction of Nuclear FactorKappaB (NF-κB) and poor clinical outcome [6]. The precise role of FADD in these cancers is not well understood. Here we aimed to elucidate its role in cancer by using a genetically engineered mouse model, which allowed for tissue specific FADD deletion simultaneous to activation of oncogenic Kras. This model enabled evaluation of differential lung cancer development in the presence or absence of FADD expression. Infecting the lungs with adenovirus expressing Cre recombinase allowed for inducible excision of FADD simultaneous to Kras activation. After treatment with Cre recombinase, mice consistently developed lung tumors in the presence of FADD expression, while in mice wherein FADD was simultaneously deleted, tumor progression was inhibited. In addition, fibroblasts isolated from FADD deficient lungs grew more slowly in culture than fibroblasts from lung tissue expressing FADD. These findings support our hypothesis that FADD is required for lung tumor cell growth and provide impetus for targeting FADD as a therapeutic for lung adenocarcinoma.