Down‐regulated expression of the TSAP6 protein in liver is associated with a transition from cirrhosis to hepatocellular carcinoma

Caillot, Frédérique; Daveau, Romain; Daveau, Maryvonne; Lubrano, Jean; Saint-Auret, Gaëlle; Hiron, Martine; Goria, Odile; Scotté, Michel; Audigier, François; Salier, Jean‐Philippe

doi:10.1111/j.1365-2559.2009.03224.x

Cited by 15 publications

(20 citation statements)

References 19 publications

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“…In addition, TSAP6 inhibits cancer growth by inducing apoptosis through a caspase-3 dependent pathway and by interaction with Nix, a pro-apoptotic Bcl-2-related protein (Zhang et al, 2001;Passer et al, 2003). Reduced expression of TSAP6 protein has been found in the transition from cirrhosis tissues to hepatocellular carcinoma (HCC), suggesting a decrease in the apoptotic process during the development of HCC (Caillot et al, 2009). Furthermore, TSAP6 has been described as a marker expressed differently in comparative gene expression profiles of smoker and nonsmoker populations in squamous cell lung cancer and in Crohn's disease (Boelens et al, 2009;Nielsen et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Analysis of exosome release and its prognostic value in human colorectal cancer

Silva

Garcı́a

Rodríguez

et al. 2011

Genes Chromosomes & Cancer

260

186

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A significant proportion of extracellular nucleic acids in plasma circulate highly protected in tumor-specific exosomes, but it is unclear how the release of exosomes is modulated in carcinogenesis. We quantified by cytometry exosomes in plasma of 91 colorectal cancer patients to evaluate their potential as a tumor indicator and their repercussions on diagnosis and prognosis. We examined the involvement of TSAP6, a TP53-regulated gene involved in the regulation of vesicular secretion, in levels of circulating exosomes in plasma of colorectal patients and in HCT116 TP53-(wild-type and null) human colorectal cancer cell lines. The fraction of exosomes in cancer patients was statistically higher than in healthy controls (mean rank ¼ 53.93 vs. 24.35). High levels of exosomes in plasma of patients correlated with high levels of carcino-embryonic antigen (P ¼ 0.029) and with poorly differentiated tumors (P ¼ 0.039) and tended to have shorter overall survival than patients with low levels (P ¼ 0.056). Release of exosomes did not correlate with TSAP6 expression; and regulation of TSAP6 by TP53 was not shown either in tumor samples or in HCT116 cell lines. Although it was not suggested that the TP53/TSAP6 pathway regulates the release of exosomes into the plasma of colorectal cancer patients, the level of circulating exosomes may be used as a tumor indicator, because it correlates with poor prognosis parameters and shorter survival.

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Section: Introductionmentioning

confidence: 99%

Analysis of exosome release and its prognostic value in human colorectal cancer

Silva

Garcı́a

Rodríguez

et al. 2011

Genes Chromosomes & Cancer

260

186

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“…8 Hitherto, STEAP3/TSAP6 had not been shown to be associated with any human disease other than liver cancer. 9 Inherited hypochromic anemia constitutes a genetically heterogeneous group of disorders resulting either from a defect in globin synthesis, as in thalassemias, or from a defect in heme synthesis. In the latter case, the genes currently known to be involved account for only a fraction of the cases, and include genes encoding enzymes of the heme biosynthesis pathway, and proteins controlling the availability of iron to the erythroid precursors.…”

Section: Introductionmentioning

confidence: 99%

A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene

Grandchamp

Hetet

Kannengiesser

et al. 2011

Blood

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STEAP3/TSAP6 encodes a ferrireductase that is involved in the acquisition of iron by developing erythroblasts and steap3/ tsap6 null-mice display severe microcytic anemia. We report a family in which 3 siblings born to healthy parents display transfusion-dependent hypochromic anemia. A nonsense STEAP3/TSAP6 was identified in the siblings at the heterozygous state. This mutation was inherited from their father while no mutation was found in their mother. A large variability of expression was found between normal alleles in a control population, confirming a previous report that STEAP3/TSAPS6 is an expressed quantitative trait locus (e-QTL). Determination of the relative allele expression showed that the "normal" allele was expressed at a significantly higher level in the father than in the affected siblings relative to the shared mutated allele. The blood level of STEAP3/ TSAP6 mRNA was severely reduced in the siblings, while both parents were in the lower range of normal controls. The STEAP3/TSAP6 protein was also reduced in lymphocytic cell lines from the patients. Collectively, our data support the hypothesis that STEAP3/TSAP6 deficiency leads to severe anemia in the affected siblings and results from the combination of a mutated allele inherited from their father and a weakly expressed allele inherited from their mother. (Blood. 2011;118(25):6660-6666)

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“…Therefore, analysis of STEAP3 expression levels could help identify the transition from HCC-free cirrhosis into a cancer-developing liver. Therefore, the use of STEAP3 as a new marker for hepatic carcinogenesis should be taken into account (69,70). Furthermore, as STEAP3 is highly expressed in fetal liver and has an important role in hemoglobin production in erythroid precursors, it could be of interest to investigate whether STEAP3 could be considered as a marker of viability for fetal development and for other types of anemia besides the recessively inherited hypochromic microcytic anemia (3).…”

Section: Steap Proteins As Biomarkers Of Diseasementioning

confidence: 99%

“…69,70). Of the different causes that lead to hepatocellular carcinoma, hepatitis B and C virus, chronic alcohol abuse, and cirrhosis are the most common (71).…”

Section: Steap Proteins As Biomarkers Of Diseasementioning

confidence: 99%

STEAP Proteins: From Structure to Applications in Cancer Therapy

Gomes

Maia²,

Santos³

2012

Molecular Cancer Research

174

214

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The human 6-transmembrane epithelial antigen of prostate (STEAP) family comprises STEAP1, STEAP2, STEAP3, and STEAP4. All of these proteins are unique to mammals and share an innate activity as metalloreductases, indicating their importance in metal metabolism. Overall, they participate in a wide range of biologic processes, such as molecular trafficking in the endocytic and exocytic pathways and control of cell proliferation and apoptosis. STEAP1 and STEAP2 are overexpressed in several types of human cancers, namely prostate, bladder, colon, pancreas, ovary, testis, breast, cervix, and Ewing sarcoma, but their clinical significance and role in cancer cells are not clear. Still, their localization in the cell membrane and differential expression in normal and cancer tissues make STEAP proteins potential candidates as biomarkers of several cancers, as well as potential targets for new immunotherapeutic strategies for disease attenuation or treatment. This review brings together the current knowledge about each STEAP protein, giving an overview of the roles of this family of proteins in human physiology and disease, and analyzes their potential as immunotherapeutic agents in cancer research. Mol Cancer Res; 10(5); 573-87. Ó2012 AACR. IntroductionThe 6-transmembrane epithelial antigen of prostate (STEAP) family of proteins includes 4 members, named 6-transmembrane epithelial antigen of prostate 1 to 4 (STEAP1-STEAP4). They all have in common a 6-transmembrane domain, a COOH-terminal domain with significant homology to the yeast FRE family of b-type cytochrome metalloreductases, and an N-terminal with homology to the archaeal and bacterial F 420 H 2 :NADP

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Down‐regulated expression of the TSAP6 protein in liver is associated with a transition from cirrhosis to hepatocellular carcinoma

Cited by 15 publications

References 19 publications

Analysis of exosome release and its prognostic value in human colorectal cancer

Analysis of exosome release and its prognostic value in human colorectal cancer

A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene

STEAP Proteins: From Structure to Applications in Cancer Therapy

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