The Role of PRP4K as a Tumor Suppressor in Lewis Lung Carcinoma Cells

Abstract

Although originally identified as a splicing kinase, recent data indicates that pre-mRNA processing factor kinase 4 (PRP4K) may promote metastasis by a partial epithelial-to mesenchymal transition (EMT) phenotype. Thus, the objective of this project was to determine the effects of PRP4K loss on lung cancer progression and metastasis in vivo. In this thesis, I showed that knockdown (KD) of PRP4K results in a stem-like phenotype in lung adenocarcinoma cells both in vitro and in vivo. I also found that PRP4K KD resulted in a partial EMT phenotype and resulted in decreased sensitivity to the cancer stem cell targeting compound retinoic acid. I further found that PRP4K KD may induce its phenotype by modulating hyaluronic acid synthesis in these cells. Taken together, these data support the hypothesis that PRP4K is acting a tumor suppressor in lung cancer cells both in vitro as well as in vivo.