Lipocalin-2 negatively modulates the epithelial-to-mesenchymal transition in hepatocellular carcinoma through the epidermal growth factor (TGF-beta1)/Lcn2/Twist1 pathway

• DOI: 10.1002/hep.26467
• Publication Date: 2013-05-20T21:46:53Z
• Authors: Yun-Peng Wang; Goung-Ran Yu; Mi-Jin Lee; Sang-Yeop Lee; In-Sun Chu; Sun-Hee Leem; Dae-Ghon Kim
• Keywords: 0301 basic medicine; Carcinoma, Hepatocellular; Epithelial-Mesenchymal Transition; Liver Neoplasms; Down-Regulation; Mice, Nude; Nuclear Proteins; In Vitro Techniques; Lipocalins; Disease Models, Animal; Mice; 03 medical and health sciences; Phenotype; Lipocalin-2; Cell Line, Tumor; Disease Progression; Animals; Heterografts; Humans; Neoplasm Invasiveness; Acute-Phase Proteins; Cell Proliferation

Lipocalin-2 (Lcn2) is preferentially expressed in hepatocellular carcinoma (HCC). However, the functional role of Lcn2 HCC progression still poorly understood, particularly with respect to its involvement invasion and metastasis. The purpose this study was investigate whether associated epithelial-mesenchymal transition (EMT) elucidate underlying signaling pathway(s). well-differentiated versus liver cirrhosis tissues, expression positively correlated stage HCC. characteristics EMT were reversed by adenoviral transduction into SH-J1 cells, including down-regulation N-cadherin, vimentin, alpha-smooth muscle actin, fibronectin, concomitant up-regulation CK8, CK18, desmoplakin I/II. Knockdown short hairpin RNA (shRNA) HKK-2 cells expressing high levels EMT. Epidermal growth factor (EGF) or transforming beta1 (TGF-β1) treatment resulted Lcn2, accompanied an increase Twist1 cells. Stable reduced expression, inhibited cell proliferation vitro, suppressed tumor metastasis a mouse model. Furthermore, EGF TGF-β1 barely changed marker ectopically Lcn2. Ectopic induced even indicating that functions downstream factors upstream Twist1.Together, our findings indicate can negatively modulate through (or TGF-β1)/Lcn2/Twist1 pathway. Thus, may be candidate suppressor potential therapeutic target