Phosphoinositide signal transduction pathway and osteosarcoma metastases

Metastasis spreading confers worse prognosis to the clinical outcome in patients affected with osteosarcoma, the most common primary bone tumour in childhood and adolescence. The identification of the molecules involved in spreading might help to understand the mechanisms of tumour dissemination, opening the way to novel therapeutic strategies. The activation of ezrin-radixin-moesin (ERM) family proteins was suggested to occur after interaction with molecules belonging to Phosphoinositide signal transduction pathway. The Phosphatydil inositol (4,5) bisphosphate (PIP2), a crucial molecule in PI pathway, was indicated to be involved in the stabilization of ERM proteins or a more efficient receptor binding. The levels of PIP2 in the pathway represent a critical element for regulation of a number of cell events. PIP2 levels are regulated by means of enzymes, including the PI-specific Phospholipase C family. The reduction of PIP2 levels induces ERM protein dissociation from the membrane. PI-PLC enzymes contribute to regulate this event. The role of PI signal transduction molecules in osteosarcoma metastases will be discussed.