Vascular invasion is one of the clinicopathologic features that are associated with early recurrence of human hepatocellular carcinoma (HCC). In this study, we have employed high-density Affymetrix oligonucleotide GeneChips (Affymetrix, Santa Clara, CA) to compare the expression profiles of HCC with and without vascular invasion. Data mining of the gene expression database established revealed that leukocyte cell-derived chemotaxin-2 (LECT2) transcripts were downregulated in HCC patients with vascular invasion. Expression of LECT2 in human HCC biopsies was significantly reduced (Po0.0001, fold change ¼ À7.2) when compared with non-tumorous adjacent liver tissues. The reduction of LECT2 expression was significantly correlated with the early recurrent and poor prognosis of the patient (P ¼ 0.024). To validate the ability of LECT2 to repress the growth of HCC, an adenoviral vector encoding the secreted human LECT2 (AdLECT2) was introduced into the human HCC cell lines Hep3B and PLC/PRF/5, which do not express endogenous LECT2. Over-expression of LECT2 resulted in the significant inhibition of in vitro migration and invasion of the AdLECT2-transfected HCC cells. Additionally, over-expression of AdLECT2 in subcutaneous Hep3B tumor xenografts in athymic nude mice resulted in significant inhibition of tumor growth (Po0.05). In summary, our data not only demonstrated that LECT2 is a candidate prognostic marker of human HCC, but also that therapeutic strategies targeting LECT2 expression is a promising therapy for human HCC.

RKIP is a member of the phosphatidylethanolamine binding protein (PEBP) family with over 400 members. Previous work showed that phosphorylation of S153 was sufficient to alter RKIP binding partners, effectively upregulating the MAP kinase and β‐adrenergic receptor signaling pathways (Granovsky and Rosner, Cell Res., 18:452, 2008). Yet little is known regarding the mechanism by which RKIP phosphorylation regulates these key signaling pathways. Here we propose a three state allosteric model to explain RKIP function. Using NMR, we demonstrate that the RKIP phospho‐switch is associated with a major structural change that can be instigated by breaking a single salt bridge. We also demonstrate that RKIP can dimerize as a result of the phospho‐switch due to formation of disulfide linkages and the functional significance of this oligomerization will be presented. Together these results reveal a novel phospho‐switch that regulates RKIP function and has broad applicability to other PEBP family members throughout evolution.