Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells

摘要: Lysophosphatidic acid (LPA), a blood-borne lipid mediator, is present in elevated concentrations ascites of ovarian cancer patients and other malignant effusions. LPA potent mitogen cells. The mechanism linking signal to cell proliferation not well understood. Little known about whether affects glucose metabolism accommodate rapid Here we describe that cells, enhances glycolytic rate lactate efflux. A real time PCR-based miniarray showed hexokinase II (HK2) was the most dramatically induced gene promote glycolysis LPA-treated Analysis human HK2 promoter identified sterol regulatory element-binding protein as primary mediator LPA-induced transcription. effects on rely LPA2, an receptor subtype overexpressed many malignancies. We further examined general role growth factor-induced proliferation. Like LPA, epidermal factor (EGF) elicited robust proliferative responses Insulin-like 1 (IGF-1) insulin, however, potently stimulated but only modestly glycolysis. Consistent with their differential glycolysis, EGF-dependent highly sensitive inhibition while growth-promoting effect IGF-1 or insulin more resistant. These results indicate LPA- EGF-induced selectively involves up-regulation metabolism. work first implicate signaling promotion