by Elizabeth Tran, Department of Biochemistry, Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana, USA
Small cell lung cancer (SCLC) accounts for more than 30,000 cases per year in the United States. Although this represents a small fraction (15%) of total lung cancer cases, SCLC stands apart from the more common, non-small cell lung cancer due to its rapid metastasis, high mortality rate (9-month median survival), heterogeneous nature, and lack of effective treatments. Importantly, while SCLC is responsive to initial chemotherapies, ~90% of patients relapse within one year due to the development of chemoresistance.
My laboratory is most well-known for contributions to the DEAD-box RNA helicase field through studies of the budding yeast DEAD-box protein Dbp2. A major tenet of our research is the constant expansion of our “toolbox”, enabling a mechanistic exploration of these enzymes with insights into roles in gene expression and relationships to cellular physiology. Moreover, our focus on Dbp2 has yielded key, unanticipated insights between resolution of RNA secondary structure, suppression of R-loops, and transcription termination.
We recently discovered that DDX5, the human ortholog of Dbp2, is overexpressed in SCLC and that knockdown of DDX5 in SCLC cells impairs energy production, mitochondrial function, and cell growth. Interestingly, Dbp2 is also required for energy production in budding yeast, indicative of an evolutionary conservation of function. We are now exploring the role of DDX5 in SCLC and in non-transformed cells, using our prior work on Dbp2 to inform our current studies. Current progress and remaining open questions will be presented.