Phosphoinositide Signal Transduction Pathway and Osteosarcoma Metastases

Metastasis spreading confers a worse prognosis to the clinical outcome among patients suffering from osteosarcoma, the most common primary bone tumor in childhood and adolescence. The detection of molecules involved in metastasis spreading might contribute to understanding tumor dissemination mechanisms, thereby opening the way to novel therapeutic strategies. The Ezrin-radixin-moesin (ERM) family proteins are activated after interacting with molecules belonging to the phosphoinositide signal transduction pathway. The phosphatydil inositol (4,5) bisphosphate (PIP2), a crucial molecule in the PI pathway, stabilizes the ERM proteins or a more efficient receptor binding. The PIP2 levels in the pathway are a critical element for regulating several cell events. The PIP2 levels are regulated using enzymes, including the PI-specific Phospholipase C family. A decrease in the PIP2 levels induces the dissociation of the ERM protein from the membrane. In this regard, the PI-PLC enzymes regulate this event. In this paper, the role of the PI signal transduction molecules in osteosarcoma metastases is discussed.