Poster Presentation 28th Lorne Cancer Conference 2016

Exosomes secreted by PI3K signaling pathway activated colorectal cancer cells mediate cell proliferation (#183)

Michael Liem 1 , Suresh Mathivanan 1
  1. La Trobe University, Melbourne/Bundoora, VIC, Australia

PI3K signalling pathway regulates a large array of cellular processes including cell cycle, proliferation, migration and inhibition of apoptosis. Dysregulation of PI3K signalling pathway leads to sustained proliferative signals thereby allowing the cells susceptible to cancer. In the case of colorectal cancer (CRC), the role of PI3K/Akt/mTOR signalling pathway is well established and remains one of the primary therapeutic target. Recent epidemiological studies suggest that diabetes and obesity increases the risk of CRC and lowers the CRC patient survival rate. An important attribute in diabetes and obesity is the presence of high levels of growth factors including insulin in blood which can activate the PI3K signalling pathway. Exosomes, secreted nanovesicles of endocytic origin, are implicated in mediating the transfer of oncogenic signals in the tumour microenvironment. However, the role of exosomes secreted by PI3K signalling activated CRC cells in the tumour microenvironment is currently unknown. To understand the role of exosomes released by PI3K signaling activated cells, exosomes were isolated from insulin-induced LIM1215 CRC cells. Label-free quantitative proteomics analysis of non-induced and insulin-induced cell secreted exosomes revealed 712 differentially abundant proteins. A network-based bioinformatics analysis highlighted the enrichment of proteins implicated in the metabolism of nucleotides, translation, ribosome biosynthesis and splicing in insulin-induced cell secreted exosomes. Consistent with the proteomic analysis, when exosomes secreted by PI3K signaling activated cells were incubated with CRC cells, it increased the cellular proliferation by two fold. Overall, the findings from this study suggest the ability of exosomes in mediating cell proliferation in neighboring cells through the regulation of protein synthesis.