N-Acetylglucosamine 6-O-sulfotransferase-2 as a tumor marker for uterine cervical and corpus cancer

Seko, Akira; Kataoka, Fumio; Aoki, Daisuke; Sakamoto, Masaru; Nakamura, Toshiaki; Hatae, Masayuki; Yonezawa, Suguru; Yamashita, Katsuko

doi:10.1007/s10719-008-9227-4

Cited by 11 publications

(9 citation statements)

References 26 publications

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“…High levels of the hHS6ST2 transcript were also detected in PANC-1 cells, a human PC cell line widely used for studying cancer biology ( Figures 1A and 1B). Our data and a previous report that hHS6ST2 was a tumour marker for uterine cervical and corpus cancer [17] suggested that it was imperative to elucidate the effect of the re-activation of this embryonic gene in cancer. To explore the role of hHS6ST2 in pancreatic tumorigenesis, shRNA (short hairpin RNA) methodology was used to silence the expression of hHS6ST2.…”

Section: Results Hhs6st2 Is Up-regulated In Human Pcsupporting

confidence: 59%

Silencing of hHS6ST2 inhibits progression of pancreatic cancer through inhibition of Notch signalling

Song

Peng

et al. 2011

Biochemical Journal

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Many of the ligands involved in developmental processes require HS (heparan sulfate) to modulate signal transduction. hHS6ST2 (human heparan sulfate D-glucosaminyl 6-O-sulfotransferase-2) is a Golgi-resident enzyme that usually acts on GlcA/IdoA(2S)-GlcNAc/NS disaccharide-6-sulfate modifications within the HS sequence. Emerging evidence indicates the importance of 6-O-sulfation in a number of developmental processes. However, any correlation with cancer-related events remains largely unexplored. In the present study, we found that hHS6ST2, but not other variants, was activated in human PC (pancreatic cancer). shRNA (short hairpin RNA)-mediated silencing of endogenous hHS6ST2 expression in the PC cell line PANC-1 inhibited cell invasion and migration. hHS6ST2 knockdown also resulted in markedly reduced tumorigenesis in immunocompromised mice. To specifically explore the molecular alterations resulting from depletion of hHS6ST2-generated 6-O-sulfation, we employed two-dimensional gel electrophoresis technology followed by nano-HPLC-ESI (electrospray ionization)-tandem MS to separate and identify total proteins from PC cells. Our data suggest that hHS6ST2 potentiates Notch signalling in PC cells. We also identified a role for hHS6ST2 in the growth and tumorigenicity of these cells which, at least in part, acts through Notch-mediated EMT (epithelial-mesenchymal transition) and angiogenesis. The results of the present study suggest that hHS6ST2 could be an attractive target for PC therapy.

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Section: Results Hhs6st2 Is Up-regulated In Human Pcsupporting

confidence: 59%

Silencing of hHS6ST2 inhibits progression of pancreatic cancer through inhibition of Notch signalling

Song

Peng

et al. 2011

Biochemical Journal

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“…These findings indicate that CHST4 has an important biological function and prognostic value in HBV-HCC. Indeed, previous studies show that CHST4 can flow in the bloodstream in soluble form (21); however, whether CHST4 can be used as a serological indicator of HBV-HCC requires further research. Moreover, as the relationship between the expression level of CHST4 and HBV-HCC prognosis was contradictory to the prognosis of HCC from TCGA, the role of CHST4 in other subtypes of HCC should also be further investigated.…”

Section: Discussionmentioning

confidence: 99%

“…For example, CHST4 is highly expressed in mucinous adenocarcinomas (18,19), where it adds sulfate to extended core 1-and core 2-based-glycans (20). Additionally, in those with early-stage uterine corpus and cervical cancer, serum CHST4 expression was higher than that of cancer antigen 125 (CA125) and squamous cell carcinoma antigen (SCC) (21). CHST4 expression is also elevated in gastric cancer tissues (22), urothelial bladder carcinoma (23), cholangiolocellular carcinoma (24), and Opisthorchis viverrini (OV)-related intrahepatic cholangiocarcinoma (25), and the CHST4 promoter is hypermethylated in HBV-HCC (26).…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate Sulfotransferase 4 Inhibits the Progression of Hepatitis B Virus-Related Hepatocellular Carcinoma and Is a Potential Prognostic Marker in Several Tumors

et al. 2020

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Carbohydrate sulfotransferase 4 (CHST4) plays an important role in lymphocyte homing and is abnormally expressed in several cancer types; however, its precise function in tumor development and progression is unknown. Here we confirm that CHST4 is aberrantly expressed in various tumor subtypes. In particular, we found that CHST4 expression was downregulated in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) tumors compared to paired normal tissue. We also showed that CHST4 overexpression inhibited the proliferation and metastasis of HCC cells in vitro. Clinically, CHST4 was identified as an independent prognostic factor for HBV-HCC patients. We further illuminated the anti-tumor role and mechanism of CHST4 in HBV-HCC by constructing a FENDRR-miR-10b-5p-CHST4 competing endogenous RNA network. We found that downregulation of CHST4 expression may promote HBV expression and regulate ribonucleoprotein complex biogenesis to promote malignant behaviors in HBV-HCC. CHST4 may also recruit CD4+ T cells, macrophages, dendritic cells, and neutrophils into the tumor microenvironment to inhibit the progression of HBV-HCC. Overall, our findings suggest that CHST4 acts as a tumor suppressor in HCC-HBV and represents a potential diagnostic and therapeutic target.

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“…2004 ) and its disruption in mice affects lymphocyte trafficking ( Hemmerich, Bistrup, et al 2001 ). CHST4 is also expressed in early-stage uterine cervical and corpus cancers ( Seko et al. 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Reconstruction of the Carbohydrate 6-O Sulfotransferase Gene Family Evolution in Vertebrates Reveals Novel Member, CHST16, Lost in Amniotes

Daza

Haitina

2019

Genome Biology and Evolution

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Abstract Glycosaminoglycans are sulfated polysaccharide molecules, essential for many biological processes. The 6-O sulfation of glycosaminoglycans is carried out by carbohydrate 6-O sulfotransferases (C6OSTs), previously named Gal/GalNAc/GlcNAc 6-O sulfotransferases. Here, for the first time, we present a detailed phylogenetic reconstruction, analysis of gene synteny conservation and propose an evolutionary scenario for the C6OST family in major vertebrate groups, including mammals, birds, nonavian reptiles, amphibians, lobe-finned fishes, ray-finned fishes, cartilaginous fishes, and jawless vertebrates. The C6OST gene expansion likely started early in the chordate lineage, giving rise to four ancestral genes after the divergence of tunicates and before the emergence of extant vertebrates. The two rounds of whole-genome duplication in early vertebrate evolution (1R/2R) only contributed two additional C6OST subtype genes, increasing the vertebrate repertoire from four genes to six, divided into two branches. The first branch includes CHST1 and CHST3 as well as a previously unrecognized subtype, CHST16 that was lost in amniotes. The second branch includes CHST2, CHST7, and CHST5. Subsequently, local duplications of CHST5 gave rise to CHST4 in the ancestor of tetrapods, and to CHST6 in the ancestor of primates. The teleost-specific gene duplicates were identified for CHST1, CHST2, and CHST3 and are result of whole-genome duplication (3R) in the teleost lineage. We could also detect multiple, more recent lineage-specific duplicates. Thus, the vertebrate repertoire of C6OST genes has been shaped by gene duplications and gene losses at several stages of vertebrate evolution, with implications for the evolution of skeleton, nervous system, and cell–cell interactions.

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N-Acetylglucosamine 6-O-sulfotransferase-2 as a tumor marker for uterine cervical and corpus cancer

Cited by 11 publications

References 26 publications

Silencing of hHS6ST2 inhibits progression of pancreatic cancer through inhibition of Notch signalling

Silencing of hHS6ST2 inhibits progression of pancreatic cancer through inhibition of Notch signalling

Carbohydrate Sulfotransferase 4 Inhibits the Progression of Hepatitis B Virus-Related Hepatocellular Carcinoma and Is a Potential Prognostic Marker in Several Tumors

Reconstruction of the Carbohydrate 6-O Sulfotransferase Gene Family Evolution in Vertebrates Reveals Novel Member, CHST16, Lost in Amniotes

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