Changes of cell shape are required for several cellular functions, including migration, and occur through cytoskeletal rearrangement induced by mechanical forces and biochemical signals. Such remodelling involves changes in activation/localisation of several proteins and lipids. In this project, we will combine biochemical and biophysical studies to investigate the link between a group of phospholipids named phosphoinositides [PIs] and changes in cellular environment/modulation of mechanical forces during cell migration. Furthermore, as genetic alterations of enzymes that regulate PIs levels occur in pathological conditions, including cancer, we will determine how such alterations impact on cytoskeletal remodelling and mechanical forces, ultimately affecting migration.
Mavrommati I, Cisse O, Falasca M, Maffucci T. Novel roles for class II Phosphoinositide 3-Kinase C2β in signalling pathways involved in prostate cancer cell invasion. Sci Rep. 2016 Mar 17;6:23277.
Costa P, Blowes LM, Laly AC, Connelly JT. Regulation of collective cell polarity and migration using dynamically adhesive micropatterned substrates. Acta Biomater. 2021;126:291-300
Kenny FN, Drymoussi Z, Delaine-Smith R, Kao AP, Laly AC, Knight MM, Philpott MP, Connelly JT. Tissue stiffening promotes keratinocyte proliferation through activation of epidermal growth factor signaling. J Cell Sci. 2018 May 16;131(10).
Maffucci T, Cooke FT, Foster FM, Traer CJ, Fry MJ, Falasca M. Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration. J Cell Biol. 2005 Jun 6;169(5):789-99.
Maffucci T. An introduction to phosphoinositides. Curr Top Microbiol Immunol. 2012;362:1-42.