gd3 synthase overexpression sensitizes hepatocarcinoma cells to hypoxia and reduces tumor growth by suppressing the csrcnf-κb survival pathwaygd3合酶过度糖分会让肝癌细胞缺氧,降低肿瘤的生长通过抑制csrcnf-κb生存途径.pdfVIP
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gd3 synthase overexpression sensitizes hepatocarcinoma cells to hypoxia and reduces tumor growth by suppressing the csrcnf-κb survival pathwaygd3合酶过度糖分会让肝癌细胞缺氧,降低肿瘤的生长通过抑制csrcnf-κb生存途径
GD3 Synthase Overexpression Sensitizes Hepatocarcinoma Cells to Hypoxia and Reduces Tumor Growth by Suppressing the cSrc/NF-kB Survival Pathway 1,2 1 1 ´ 1 2 Josep M. Lluis , Laura Llacuna , Claudia von Montfort , Cristina Barcena , Carlos Enrich , Albert 1. ´ 1,3. Morales *, Jose C. Fernandez-Checa * 1 Department of Cell Death and Proliferation, IIBB-CSIC, and Liver Unit, Hospital Clinic, IDIBAPS-CIBEK, CIBEREHD, Barcelona, Spain, 2 Departament de Biologia Cellular, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain, 3 Research Center for Alcoholic Liver and Pancreatic Diseases, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States of America Abstract Background: Hypoxia-mediated HIF-1a stabilization and NF-kB activation play a key role in carcinogenesis by fostering cancer cell survival, angiogenesis and tumor invasion. Gangliosides are integral components of biological membranes with an increasingly recognized role as signaling intermediates. In particular, ganglioside GD3 has been characterized as a proapoptotic lipid effector by promoting cell death signaling and suppression of survival pathways. Thus, our aim was to analyze the role of GD3 in hypoxia susceptibility of hepatocarcinoma cells and in vivo tumor growth. Methodology/Principal Findings: We generated and characterized a human hepatocarcinoma cell line stably expressing GD3 synthase (Hep3B-GD3), which catalyzes the synthesis of GD3 from GM3. Despite increased GD3 levels (2–3 fold), no significant changes in cell morphology or growth were observed in Hep3B-GD3 cells compared to wild type Hep3B cells under normoxia.
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