Free Choline Influences Adaptation Mechanisms in Choline Phospholipid Metabolism of Human Breast Cancer Cells

Balaji Krishnamachary¹, Noriko Mori¹, Mayur Gadiya¹, Yelena Mironchik¹, Flonne Wildes¹, Kristine Glunde¹, Zaver M. Bhujwalla¹

Synopsis: Increased phosphocholine (PC) and total choline are consistently observed in cancers, especially breast cancer. Only now are we beginning to uncover the complexity of factors that regulate choline metabolism in cancer, and the compensatory mechanisms that exist in this pathway. Here we have shown the interdependence between two enzymes in choline metabolism, choline kinase (Chk) the enzyme that forms phosphocholine from free choline, and phosphatidylcholine-specific phospholipase D1 (PLD1), the enzyme that forms choline from phosphatidylcholine. We have also identified increased free choline as an inhibitor of the increase of PLD1 observed following Chk downregulation.