Hypoxia increases cytoplasmic expression of NDRG1, but is insufficient for its membrane localization in human hepatocellular carcinoma

• Published in: FEBS letters 2007-03, Vol.581 (5), p.989-994
• Main Authors: Sibold, Sonja, Roh, Vincent, Keogh, Adrian, Studer, Peter, Tiffon, Céline, Angst, Eliane, Vorburger, Stephan A., Weimann, Rosemarie, Candinas, Daniel, Stroka, Deborah
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Carcinoma, hepatocellular; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell Membrane - metabolism; Cytoplasm - metabolism; dimethyloxallyl glycine; DMOG; Gene Expression; glycogen synthase kinase 3; GSK3; HCC; hepatocellular carcinoma; HIF-1; Humans; Hypoxia; Hypoxia - metabolism; Hypoxia-Inducible Factor 1, alpha Subunit - chemistry; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; hypoxia-inducible factor-1; In Vitro Techniques; Intracellular Signaling Peptides and Proteins - chemistry; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Male; Mice; Mice, Nude; Molecular Sequence Data; N-myc downstream regulated gene-1; NDRG1; Neoplasm Transplantation; oxygen; Protein Structure, Tertiary; serum- and glucocorticoid-induced kinase 1; SGK-1; short-interfering RNA; siRNA; Transplantation, Heterologous
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2007.01.080

NDRG1 is a hypoxia-inducible protein, whose modulated expression is associated with the progression of human cancers. Here, we reveal that NDRG1 is markedly upregulated in the cytoplasm and on the membrane in human hepatocellular carcinoma (HCC). We demonstrate further that hypoxic stress increases the cytoplasmic expression of NDRG1 in vitro, but does not result in its localization on the plasma membrane. However, grown within an HCC-xenograft in vivo, cells express NDRG1 in the cytoplasm and on the plasma membrane. In conclusion, hypoxia is a potent inducer of NDRG1 in HCCs, albeit requiring additional stimuli within the tumour microenvironment for its recruitment to the membrane.