Miss Natalia Haddad

Research project: Developing novel therapeutic agents against serotonin receptor signalling in colorectal cancer

Abstract

The Hippo Signaling Pathway is an evolutionary conserved pathway with a key role as a regulatory pathway in organ growth control and maintenance. Serotonin (5-hydroxytryptamine, 5-HT) is a classical neurotransmitter in the central nervous system which is also known as a local mediator in the gastrointestinal tract. Serotonin as also been recently implicated as a potent growth factor for several human cancers. Serotonin is thought to encourage cancer cell proliferation, metastasis, and formation of tumour blood supply initiation (angiogenesis). As potentiation of serotonin signalling results

in enhanced intestinal epithelial proliferation and as YAP/TAZ are key proteins in encouraging cancer proliferation and inhibition of apoptosis as well, then it is an obvious pathway to investigate and weather 5HT2b receptor regulation crosstalk's with YAP/TAZ and the Hippo signalling pathway. The aims of this project are to elucidate the link between cancer receptor signalling primarily mediated by 5-HT2b by using therapeutic targets which may act as antagonists of these receptors. The second aim of this project is to analyse if 5-HT2b and any effect on signalling may be mediated by the Hippo Signalling Pathway and whether there is a crosstalk between classical cancer signalling pathways including MAPK and PI3k/AKT signalling.