Role of phospholipase C in cell invasion and metastasis.
Phospholipases are enzymes that use phospholipids as substrate and are classified in three major classes A, C and D based on the reaction they catalyse. Phosphatidylinositol-specific Phospholipase C enzymes utilize phosphatidylinositol 4,5-bisphosphate as substrate and cleave the bond between the glycerol and the phosphate to produce important second messenger such as inositol trisphosphate and diacylglycerol. The Phospholipase C members are the most well-known phospholipases for their role in lipid signalling and cell proliferation and comprise 13 isoforms classified in 6 distinct sub-families. In particular, signalling activated by Phospholipase C γ, mostly activated by receptor and non-receptor tyrosine kinases, is well characterized in different cell systems. Increasing evidence suggest that Phospholipase C γ plays a key role in cell migration and invasion. Because of its role in cell growth and invasion, aberrant Phospholipase C γ signalling can contribute to carcinogenesis. A major challenge facing investigators who seek to target Phospholipase C γ directly is the fact that it is considered an "undruggable" protein. Indeed, isoform specificity and toxicity represents a big hurdle in the development of Phospholipase C γ small molecule inhibitors. Therefore, a future development in the field could be the identification of interacting partners as therapeutic targets that could be more druggable than Phospholipase C γ.
Aging Research Centre, G. d'Annunzio University Foundation, 66013 Chieti, Italy. Electronic address: rossanolattanzio@libero.it.
Rossano
R
Lattanzio
Mauro
M
Piantelli
Marco
M
Falasca
D000818:Animals; D002465:Cell Movement; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D051966:Phospholipase C gamma / Q000235:genetics / Q000378:metabolism*
C522157:PLCG1 protein, human; D051966:Phospholipase C gamma