Thursday 12 Apr/18 at 4:00 pm - a QCRI Frontiers of Cancer Research presentation by Dr. Ian Chin-Sang
a QCRI Frontiers of Cancer Research presentation
Ian D. Chin-Sang, PhD
Professor, Dept. of Biology, Queen's University
Thursday 12 Apr/18 at 4:00 pm in QCRI 100/01 conf rms
"USING A TINY WORM TO HELP SOLVE A BIG PROBLEM LIKE CANCER"
Cancer often results when normal signal transduction pathways go awry due to the abnormal regulation or function of the genes in these pathways. A major oncogenic pathway is the Insulin and Insulin Growth Factor Signaling (IIS) pathway. IIS is an evolutionary conserved pathway from worms to humans. A very important regulator of this pathway is the tumour suppressor PTEN. PTEN is the second most (after p53) commonly lost tumour suppressor in cancers. The C. elegans orthologue of PTEN is called DAF-18 and, in a striking similarity in function, we show that C. elegans mutants that lose DAF-18/PTEN have reduced life span and have cells that divide and move when they should remain quiescent. The human PTEN gene can functionally replace the loss of worm DAF-18. We have used these phenotypes to understand upstream and downstream and potential cross talk of pathways that function with DAF-18/PTEN. We have discovered a role for DAF-18/PTEN that functions in a non-canonical IIS pathway that is independent of the terminal transcription factor FOXO. We show that that a class of insulin like peptides act on the insulin receptor to promote cell divisions and that BMP signaling functions upstream of the insulin like peptides. Chemical screening and genetics provide evidence that the energy sensor, AMPK, works downstream of IIS and blocks the function of Protein Phosphatases, PP2As. Further, we show that in the absence of DAF-18/PTEN or AMPK, PP2As promote cell divisions by activation of MPK-1/ERK via LIN-45/RAF in the MAPK signaling pathway. We have also used C. elegans IIS pathway phenotypes to provide roles for the insulin like peptides in C. elegans. We have systematically overexpressed all 40 Insulin like peptides in the C. elegans nervous system and tested for their ability to activate or inhibit the insulin receptor. We have identified in vivo functions for 30 of the 40 INS and will use this data to determine what makes an insulin like peptide an activator or inhibitor of the insulin receptor. Further advances in our understanding of these pathways, the cross talk, and their cell and tissue specificity, will help in the development of targeted therapies.
Everyone is welcome!