Human homolog of NOTUM, overexpressed in hepatocellular carcinoma, is regulated transcriptionally by β‐catenin/TCF

Torisu, Yuichi; Watanabe, Akira; Nonaka, Aya; Midorikawa, Yutaka; Makuuchi, Masatoshi; Shimamura, Tadakatsu; Sugimura, Haruhiko; Niida, Atsushi; Akiyama, Tetsu; Iwanari, Hiroko; Kodama, Tatsuhiko; Zeniya, Mikio; Aburatani, Hiroyuki

doi:10.1111/j.1349-7006.2008.00814.x

Cited by 52 publications

(52 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A small domain of notum1a expression persists in the tail after the Wnt blockade, suggesting either an area of increased notum1a transcript stability or Wnt-independent regulation. Interestingly, NOTUM is upregulated in human primary hepatocellular carcinomas with high levels of intracellular -catenin (Torisu et al, 2008). Our results show that, similar to Drosophila Notum, notum1a expression requires Wnt/-catenin signaling.…”

Section: Notum1a Identification and Expressionmentioning

confidence: 54%

“…A secreted / hydrolase, Notum, releases glypicans at their GPI anchors to restrict the spread of the Wg ligand and to inhibit its activity (Giraldez et al, 2002;Kreuger et al, 2004). Notum expression is induced by high Wg activity (Gerlitz and Basler, 2002;Torisu et al, 2008); therefore, Notum acts as part of a negative-feedback mechanism that tightly controls the extracellular distribution of the Wg ligand (Piddini and Vincent, 2009). In this work, we investigate whether Notum plays a similar role as an inhibitor of Wnt/-catenin signaling and whether it is involved in other glypican-dependent processes during vertebrate development.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A zebrafish Notum homolog specifically blocks the Wnt/β-catenin signaling pathway

2012

View full text Add to dashboard Cite

SUMMARYMultiple developmental processes require tightly controlled Wnt signaling, and its misregulation leads to congenital abnormalities and diseases. Glypicans are extracellular proteins that modulate the Wnt pathway. In addition to interacting with Wnts, these glycosophosphotidylinositol (GPI)-anchored, heparan-sulfate proteoglycans bind ligands of several other signaling pathways in both vertebrates and invertebrates. In Drosophila, Notum, a secreted /-hydrolase, antagonizes the signaling of the prototypical Wnt Wingless (Wg), by releasing glypicans from the cell surface. Studies of mammalian Notum indicate promiscuous target specificity in cell culture, but the role of Notum in vertebrate development has not been studied. Our work shows that zebrafish Notum 1a, an ortholog of mammalian Notum, contributes to a self-regulatory loop that restricts Wnt/-catenin signaling. Notum 1a does not interact with Glypican 4, an essential component of the Wnt/planar cell polarity (PCP) pathway. Our results suggest a surprising specific role of Notum in the developing vertebrate embryo.

show abstract

Section: Notum1a Identification and Expressionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

A zebrafish Notum homolog specifically blocks the Wnt/β-catenin signaling pathway

2012

View full text Add to dashboard Cite

show abstract

“…(8) GPC3 is linked to the outer surface of the cell membrane through a glycosylphosphatidylinositol anchor (9) and released from the cell surface by a lipase called notum to regulate the signaling of Wnts, hedgehogs, fibroblast growth factors (FGFs), and bone morphogenetic proteins (BMPs). (10)(11)(12)(13)(14) Depending on the cellular context, its function can be stimulatory or inhibitory activity or signaling. GPC3 plays an important role in the embryonic and fetal periods of tissue, organ formation, and developmental stages, mainly playing a negative regulatory role, preventing tissue organs from growing too large and regulating body size overall.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of Monoclonal Antibody Against Glypican-3

Wang²,

Qin³

et al. 2012

Hybridoma

View full text Add to dashboard Cite

Glypican-3 (GPC3) has been reported as a novel serum and histochemical marker for hepatocellular carcinoma (HCC) by several groups. As an oncofetal protein, it is expressed abundantly in the fetal liver, inactive in the normal adult liver, and frequently reactivated in HCC. Immunology reagents are urgently needed to proceed with mechanism-related research, clinical validation, and application. In this report, monoclonal antibodies (MAbs) against GPC3 were made from hyperimmune BALB/c mice by injecting 100 μg of purified antigen intraperitoneally. Hybridomas were screened by indirect enzyme-linked immunosorbent assay (ELISA) using purified protein. Finally 13 mouse hybridomas producing MAbs to GPC3 were established. The MAbs obtained were fully characterized using Western blot analysis, immunofluorescence, and immunohistochemistry. The results showed that these antibodies could be used for preliminary application of the next step mechanism-related research and GPC3 expression level analysis.

show abstract

“…In mammals, six members of GPCs have been reported, GPC1 to GPC6. GPCs are released from the cell surface by a lipase called Notum to regulate the signaling of Wnts, Hedgehogs, fibroblast growth factors (FGFs) and bone morphogenetic proteins (BMPs) (18)(19)(20)(21)(22)(23)(24)(25). Depending on the cellular context, their function can be stimulatory or inhibitory activity, or signaling.…”

Section: Glypican-3 Is a Useful Diagnostic Marker For A Component Of mentioning

confidence: 99%

Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer

Nakatsura¹

2009

Int J Oncol

View full text Add to dashboard Cite

Abstract. Primary liver cancers are classified into three types based on their morphology and cytogenetic characteristics hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular and cholangiocarcinoma (CHC). It is often difficult to distinguish these liver tumors. Glypican-3 (GPC3) is serological and histochemical marker of hepatocellular carcinoma. In order to separate these three types of liver cancers, we analyzed the GPC3 expression in 85 liver resection specimens, including 46 HCCs, 28 ICCs and 11 CHCs. GPC3 immunohistochemical staining was used to distinguish HCC from ICC by comparing with the conventional biomarker, ·-fetoprotein (AFP). The immunostaining of GPC3 was identified in 78.3% (36/46) of HCCs, 60% (9/15) of well differentiated, 88.9% (16/18) of moderately differentiated and 84.6% (11/13) of poorly differentiated HCCs. It was negative in the ICCs. We confirmed that GPC3 expression is specific to HCC component (8/11, 72.7%) but few samples also showed weakly in ICC component (2/11, 18.2%) of CHC sections among 11 cases compared with HCC biomarkers including AFP and hepatocyto paraffin 1 (HepPar1), and ICC biomarkers cytokeratin (CK) 7 and CK19. Three cases in which the macroscopic features resembled ICC did not express GPC3 even in the pathological HCC component. Most (10/11, 91%) of the pathological cholangiocarcinoma components in CHC showed positive staining for CK7 and CK19. The results of this study suggest that GPC3 is a biomarker that is sensitive and specific to HCC component of CHC, and CK7 and CK19 are markers for pathological cholangiocarcinoma component of CHC.

show abstract

Human homolog of NOTUM, overexpressed in hepatocellular carcinoma, is regulated transcriptionally by β‐catenin/TCF

Cited by 52 publications

References 33 publications

A zebrafish Notum homolog specifically blocks the Wnt/β-catenin signaling pathway

A zebrafish Notum homolog specifically blocks the Wnt/β-catenin signaling pathway

Preparation and Characterization of Monoclonal Antibody Against Glypican-3

Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer

Contact Info

Product

Resources

About