Elucidation of molecular mechanisms underlying the aberrant
phosphatidylcholine cycle in
cancer cells plays in favor of the use of metabolic imaging in oncology and opens the way for designing new targeted
therapies. The anomalous
choline metabolic profile detected in
cancer by magnetic resonance spectroscopy and spectroscopic imaging provides molecular signatures of
tumor progression and response to
therapy. The increased level of intracellular
phosphocholine (
PCho) typically detected in
cancer cells is mainly attributed to upregulation of
choline kinase, responsible for
choline phosphorylation in the biosynthetic Kennedy pathway, but can also be partly produced by activation of
phosphatidylcholine-specific phospholipase C (
PC-PLC). This hydrolytic
enzyme, known for implications in
bacterial infection and in plant survival to hostile environmental conditions, is reported to be activated in
mitogen- and oncogene-induced
phosphatidylcholine cycles in mammalian cells, with effects on cell signaling, cell cycle regulation, and cell proliferation. Recent investigations showed that
PC-PLC activation could account for 20-50% of the intracellular
PCho production in ovarian and
breast cancer cells of different subtypes. Enzyme activation was associated with
PC-PLC protein overexpression and subcellular redistribution in these
cancer cells compared with non-tumoral counterparts. Moreover,
PC-PLC coimmunoprecipitated with the human
epidermal growth factor receptor-2 (HER2) and EGFR in HER2-overexpressing breast and
ovarian cancer cells, while pharmacological
PC-PLC inhibition resulted into long-lasting HER2 downregulation, retarded receptor re-expression on plasma membrane and antiproliferative effects. This body of evidence points to
PC-PLC as a potential target for newly designed
therapies, whose effects can be preclinically and clinically monitored by metabolic imaging methods.