Role of G3BP1 Acetylation in Lung Cancer

Lung cancer is the leading cause of cancer mortality worldwide. The latest estimate is that approximately 221,200 people will be diagnosed with lung cancer in 2015, resulting in approximately 158,040 deaths in the United States. Targeted therapies have been developed in recent years to treat lung cancer with particular molecular markers. Better understanding of the cancer etiology and development of better screening, diagnosis and treatments are needed. The Ras GTPase-activating protein-binding protein G3BP1 is an RNA metabolism protein. High levels of G3BP1 were found to correlate with poor prognosis in lung cancer. We recently found that this protein is modified by acetylation of a specific lysine residue. We propose that this modification event promotes lung cancer progression. In Aim 1, we will determine whether the level of acetylated-G3BP1 is an even better prognostic marker for lung cancer using a new antibody that specifically recognizes this modification. In Aim 2, we will further examine the role of G3BP1 acetylation in lung cancer proliferation and metastasis. The significance of EGFR signaling in G3BP1 acetylation will also be investigated. Aim 3 is to determine the enzymes that regulate G3BP1 acetylation, providing novel therapeutic targets. The collaborative research team includes a biostatistician and a lung cancer biologist. Three shared resource facilities (Biospecimen and Tissue Procurement, Biostatistics and Bioinformatics, and Redox Metabolism) will be engaged in this project. The expected outcome of the proposed studies includes the identification of a potential biomarker, novel mechanistic insights and new molecular targets for developing future lung cancer treatments.