Discipline: Biological Sciences
Subcategory: Cancer Research
Derick N. Rosario - University of Puerto Rico, Rio Piedras Campus
Co-Author(s): Robert J. Nogard and Ben Z. Stanger, University of Pennsylvania
More than 90% of cancer related deaths are due to metastasis, a cancer cell’s ability to invade into the surrounding tissue, enter the vasculature, disseminate throughout the body, exit the vasculature, and establish secondary tumors in distant organs. The metastatic cascade is postulated to be mediated by cancer’s ability to reactivate the developmental program of epithelial-to-mesenchymal transition (EMT). We previously developed a novel system for tracking both epithelial and mesenchymal pancreatic tumor cells in a well-accepted genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDA) that allows detection and isolation of cells that have undergone EMT. We performed RNA-sequencing to characterize the transcriptional events that occur during tumor-associated EMT in vivo and found enrichment of genes that are predicted to be targets of the NFAT transcription factor. Based on these data, we propose that NFAT is a transcriptional activator of EMT in pancreatic cancer, leading to increased invasion and metastasis. Ca2+ is known to be necessary NFAT activity, and we find that cells undergoing EMT have higher cytoplasmic Ca2+ levels. The goal of this project is to determine whether calcium flux is required for EMT by chelating calcium or inhibiting calcium channels and determining the effects on epithelial-mesenchymal status.Not Submitted
Funder Acknowledgement(s): This work would not have been possible without the advice and support of Dr. Ben Z. Stanger, my mentor Robert J. Norgard, the SUIP Director Dr. Arnaldo J Diaz Vazquez and Stanger Group Lab Members. This work was funded by the MARC program, Biomedical Graduate Studies (BGS), and the Office of Research and Diversity Training - Perelman School of Medicine.
Faculty Advisor: Ben Z. Stanger, firstname.lastname@example.org
Role: I was involved in every aspect of this project.