LAT2, a Lipid Raft Protein That Participates in AKT Phosphorylation in Mantle Cell Lymphoma, Is a Target for Perifosine Chemotherapy (original) (raw)

Blood, 2014

Abstract

Introduction: Lipid rafts are highly ordered membrane domains that are enriched in cholesterol and sphingolipids and provide an environment for signal transduction proteins which control cell survival and cell death. Altered raft assembly has been implicated in cancer progression. Alkylphospholipids (APL) inhibit the AKT pathway and induce apoptosis of malignant cells but not of their normal counterparts when used at the same concentration. LAT2 (Linker for activation of T-cells family member 2) is a lipid raft component which is disrupted by APLs in leukemic cells. In the present study we evaluated the effect of perifosine, an APL with anticancer activity in humans, on the LAT2 and AKT pathways using a Mantle Cell Lymphoma (MCL) cell line (Granta-519 cells) as a model. We selected MCL cells to study because AKT is constitutively phosphorylated in this disease. Methods: We determined whether perifosine induced apoptosis of unmodified Granta-519 cells using flow cytometry, we measure...

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