Cell Signalling Group

Tumour initiation and progression result from inappropriate activation of intracellular signalling cascades.  Rho-like GTPases are molecular switches in signalling pathways that regulate cytoskeletal and junctional organisation, as well as gene transcription.  In this way, Rho proteins influence cell morphology, adhesion, motility, as well as cell cycle progression and cell survival.  Rho proteins are transforming in vitro and are essential for Ras-mediated in vitro transformation.  Moreover, data has emerged to directly implicate Rho proteins in tumour initiation and progression in vivo.  Our group investigates how the activities of certain regulators of the Rho protein Rac are controlled.  We are also identifying signalling events downstream of Rac that modulate tumour susceptibility and disease progression.

Mitotic cells in cysts – stained with actin (red), Hoescht (blue) and Tubulin (green).

MDCK cells, grown in a collagen matrix, where they form hollow spheres, called cysts. When the growth factor HGF is added to the cysts, they start to sprout, with actin-rich projections emerging from the surface of some of the cells. After one or two days, some of these cells undergo EMT, and re-orientate their axis of cell division, forming long chains of cells which can start to hollow out to form hollow tubules. This recapitulates stages in normal kidney development, and is a useful model for studying EMT and oriented cell division, and the way in which these might contribute to tumour progression. Actin is cyan, and nuclei are red.

Both images supplied by Andrew Porter, Cell Signalling.