Research Abstracts Online
January 2010 - March 2011
University of Minnesota Twin Cities
PI: Jonathan D'Cunha
Translational Control of Lung Cancer: Mechanistic Studies in Tumorigenesis
Lung cancer is a leading cause of cancer-related deaths in the U.S. and worldwide. Therefore, developing new molecular targets for lung cancer therapy remains a top priority. Non-small cell lung cancer (NSCLC) comprises 80% of all lung cancers. A growing body of evidence clearly indicates that enhanced translation is a characteristic of malignant transformation in a number of tumors, including NSCLC. Even with best standard medical and surgical therapy, the outlook for patients is often dismal upon diagnosis. Thus, molecular controls of this pathway are attractive targets for novel therapies. To this end, these researchers are interested in the molecular events following translational activation that lead to the development of NSCLC. In-depth understanding of this will potentially lead to new therapeutic approaches.
Previous work from this laboratory demonstrated that repression of enhanced translational activity in NSCLC results in reversion of the malignant phenotype in vitro and in vivo. Based on this previous work and accumulating work by others in translational control, the researchers hypothesized that enhanced translational activation is a key event in tumorigenesis in NSCLC. To better understand the important malignancy-associated proteins regulated by enhanced translational activity, they investigated the molecular mechanisms of translational activation in NSCLC by activating the translational control complex of human bronchial epithelial cells thereby rendering them tumorigenic. The tumorigenic clones were analyzed at the molecular level in vitro and in vivo. The researchers then sought to identify the key transcripts accounting for oncogenesis. Finally, they tested small molecule inhibitors of key proteins that account for tumorigenesis as a potential novel therapeutic strategy. These investigations serve as a backbone for future investigations into a much-needed new class of therapeutics for NSCLC.
Joel McCauley, Graduate Student
Scott Selby, Research Associate