Abstract #0652

The Interdependence of Choline Kinase and Phospholipase D: Adaptation Mechanisms in Choline Phospholipid Metabolism of Human Breast Cancer Cells

Balaji Krishnamachary¹, Mayur Gadiya², Noriko Mori¹, Yelena Mironchik¹, Kristine Glunde¹, Zaver M. Bhujwalla¹

¹JHU ICMIC Program, Russell H. Morgan Department of Radiology & Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States; ²JHU ICMIC Program, Russell H. Morgan Department of Radiology & Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

A hallmark of cancer is an increase of cellular phosphocholine (PC) and total choline-containing compounds (tCho), which are closely related to malignant transformation, invasion and metastasis. Enzymes in choline metabolism present attractive targets that can be exploited for treatment. Here we have shown that at least two of these enzymes are interdependent. Downregulation of choline kinase (Chk) with siRNA results in increased phospholipase D1 (PLD1) expression and downregulation of PLD1 results in increased Chk expression, typifying the ability of cancer cells to adapt. These data support multiple targeting of enzymes in the choline pathway using a multiple siRNA approach.