Research: 2018 – Avalon (Kao)

Project Title:
Characterization of a novel Myc-Pygo2 ribonucleoprotein complex that drives prostate cancer cell proliferation
Investigators:
Kenneth R. Kao, Memorial University of Newfoundland
 
Dr. Ken Kao received his education and training in cancer research from the University of Toronto, the Marine Biological Laboratory in Woods Hole, MA, U.S.A., and the University of Cambridge, U.K. He completed an NCIC fellowship at the Mount Sinai Hospital in Toronto and subsequently joined, in 1993, the Faculty of Medicine at Memorial University of Newfoundland. Dr. Kao is presently full Professor in the Terry Fox Cancer Research Labs of the Division of Biomedical Sciences, where he runs a cutting-edge research laboratory studying the molecular and cell biology of cancer at Memorial University. He is also director of the IHC cancer testing laboratory at Eastern Health. He has published numerous internationally peer-reviewed original research articles and book chapters. His research has been and continues to be supported by research grants and contracts totaling more than $3.5 million from the Canadian Institutes of Health Research, the Cancer Research Society, The Canadian Breast Cancer Foundation, and most recently from funds generated by the Motorcycle Ride for Dad administered through the Dr. H. Bliss Murphy Cancer Foundation. Dr. Kao serves on national boards and committees dedicated to
responsible research funding in the biomedical and cancer field.
Project Abstract:
Cancer cells are normal cells that have lost their ability to function in a community with other normal cells and grow in an uncontrollable way. The growth capacity of the cells is controlled by a gene called MYC (pronounced “mick”). MYC is a notorious gene that causes aggressive prostate cancer. MYC is a master-regulator that directs other genes needed to multiply a cell to become many cells. MYC combines with other proteins and a special type of molecule called RNA. RNA is traditionally known as a messenger that transmits information in genes to make proteins. But the RNA we found is important for maintaining MYC attached to its protein and RNA accessories in order to act as a carcinogenic unit. Understanding how MYC acts will give us clues about how to approach new molecule-based methods to detect growing cancer and potentially create new drugs to stop MYC.
Scientific Abstract:
The MYC family of gene transcription master regulators are an important class of proteins that effect expression of broad sets of genes associated with cell proliferation and tissue growth. When deregulated, cMyc is an important driver of prostate cancer as its increased activity from gene rearrangements predicted poor outcomes in prostate cancer patients. Identifying critical components that interact with and are required for cMyc function in prostate cancer cells is important for the development of new clinical modalities that can disrupt the interactions. We recently reported in prostate cancer cells, a novel interaction between cMyc with the Pygo2 chromatin effector that was required for mitotic gene expression. Pygo2 recruits histone acetyl Transferase (HAT)s such as CBP/p300 to genes marked for transcriptional activation by modifying chromatin structure into an open configuration, ready for transcription. Recent published findings, along with our preliminary evidence, suggest that Myc and Pygo2 interact in a complex with the long non-coding (lnc) RNAs PCGEM1 and EPIC1 in prostate cancer. To determine the Myc-Pygo2-RNA interactome in prostate cancer, we will use an unbiased RNA-protein interaction assay (RIP-seq) to confirm the involvement of EPIC1and PCGEM1 and identify novel RNAs associated with cMyc-Pygo2 containing complexes in prostate cancer cells.
Impact on prostate cancer patients:
The longevity and quality of life of prostate cancer patients have improved because of advances in basic research. This work is expected to provide insight into the molecular basis of oncogenic Myc-dependent transcriptional function, which will help provide the foundation for cancer related targeting therapies.