Hepatic adenomas: Presumed innocent until proven to be beta-catenin mutated

Monga, Satdarshan P.

doi:10.1002/hep.21110

Cited by 34 publications

(21 citation statements)

References 29 publications

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“…Alteration in Wnt/␤-catenin signaling is able to disorganize the fate of the liver and pancreas during early endoderm patterning but facilitates hepatic growth in the bud stage of mouse liver (81,88). Moreover, ␤-catenin is involved in liver development, regeneration, and cancer pathogenesis (89)(90)(91). In addition to functions in modulating various biological processes, such as cell proliferation, differentiation, and apoptosis (92), BMP signaling plays pleiotropic roles in developmental processes of several organisms, including embryonic dorsoventral patterning (93), induction of neural tissue (94), formation of joints in the skeletal system (95), and neurogenesis in the adult brain (96).…”

Section: Discussionmentioning

confidence: 99%

Nucleoporin 62-Like Protein Activates Canonical Wnt Signaling through Facilitating the Nuclear Import of β-Catenin in Zebrafish

Yang

Lin

et al. 2015

Molecular and Cellular Biology

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c Nucleoporin p62 (Nup62) localizes in the central channel of nuclear pore complexes (NPCs) and regulates nuclear pore permeability and nucleocytoplasmic transport. However, the developmental roles of Nup62 in vertebrates remain largely unclear. Zebrafish Nup62-like protein (Nup62l) is a homolog of mammalian Nup62. The nup62l gene is maternally expressed, but its transcripts are ubiquitously distributed during early embryogenesis and enriched in the head, pharynx, and intestine of developing embryos. Activation of the Wnt/␤-catenin pathway positively modulates nup62l transcription, while Bmp signaling acts downstream of Wnt/␤-catenin signaling to negatively regulate nup62l expression. Overexpression of nup62l dorsalized embryos and enhanced gastrula convergence and extension (CE) movements. In contrast, knockdown of Nup62l led to ventralized embryos, an impediment to CE movements, and defects in specification of midline organ progenitors. Mechanistically, Nup62l acts as an activator of Wnt/␤-catenin signaling through interaction with and facilitation of nuclear import of ␤-catenin-1/2 in zebrafish. Thus, Nup62l regulates dorsoventral patterning, gastrula CE movements, and proper specification of midline organ precursors through mediating the nuclear import of ␤-catenins in zebrafish.

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Section: Discussionmentioning

confidence: 99%

Nucleoporin 62-Like Protein Activates Canonical Wnt Signaling through Facilitating the Nuclear Import of β-Catenin in Zebrafish

Yang

Lin

et al. 2015

Molecular and Cellular Biology

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“…Besides prostaglandin signaling, Wnt/β-catenin activation has also been implicated in various stages of hepatic tumorigenesis(Branda and Wands 2006, Giles et al 2003, Merle et al 2004, Monga 2006, Satoh et al 2000, Thompson and Monga 2007, Zucman-Rossi et al 2006). β-catenin functions as a transcription co-factor of the T-cell factor/lymphoid enhancer factor (TCF/LEF) family and leads to the activation of Wnt target genes such as c-myc , cyclin D1 and Akt (Clevers 2006, Dihlmann et al 2005, Gordon and Nusse 2006, Hoppler and Kavanagh 2007, Moon et al 2004, Tetsu and McCormick 1999).…”

Section: Introductionmentioning

confidence: 99%

Microsomal prostaglandin E synthase-1 promotes hepatocarcinogenesis through activation of a novel EGR1/β-catenin signaling axis

Han

2011

Oncogene

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Microsomal prostaglandin E synthase-1 (mPGES-1) is a key enzyme that couples with cyclooxygenase-2 (COX-2) for the production of PGE2. Although COX-2 is known to mediate the growth and progression of several human cancers including hepatocellular carcinoma (HCC), the role of mPGES-1 in hepatocarcinogenesis is not well established. This study provides novel evidence for a key role of mPGES-1 in HCC growth and progression. Forced overexpression of mPGES-1 in two HCC cell lines (Hep3B and Huh7) increased tumor cell growth, clonogenic formation, migration and invasion, whereas knockdown of mPGES-1 inhibited these parameters, in vitro. In a SCID mouse tumor xenograft model, mPGES-1 overexpressed cells formed palpable tumors at earlier time points and developed larger tumors when compared to the control (p<0.01); in contrast, mPGES-1 knockdown delayed tumor development and reduced tumor size (p<0.01). Mechanistically, mPGES-1-induced HCC cell proliferation, invasion and migration involve PGE2 production and activation of early growth response 1 (EGR1) and β-catenin. Specifically, mPGES-1-derived PGE2 induces the formation of EGR1-β-catenin complex, which interacts with TCF4/LEF1 transcription factors and activates the expression of β-catenin downstream genes. Our findings depict a novel crosstalk between mPGES-1/PGE2 and EGR1/β-catenin signaling that is critical for hepatocarcinogenesis.

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“…1 Identification of the b-catenin mutation has proven to be of clinical significance due to its strong association for risk of HCC. 1,8,[13][14][15][16] Finally, <10% of HCA still remain unclassified. 1 An immunohistochemical (IHC) classification that allows identification of HCA subtypes has been developed that demonstrates good correlation with molecular data.…”

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confidence: 97%

Immunohistochemical Markers on Needle Biopsies Are Helpful for the Diagnosis of Focal Nodular Hyperplasia and Hepatocellular Adenoma Subtypes

Bioulac‐Sage

Cubel

Taouji

et al. 2012

American Journal of Surgical Pathology

118

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Phenotypic identification of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) subtypes using immunohistochemical markers has been developed from their molecular characteristics. Our objective was to evaluate the sensitivity of these markers in the definitive diagnosis of these lesions by core needle biopsies. A total of 239 needle biopsies paired with their surgical resection specimen (group A) or without an associated resection specimen (group B) were reviewed. Using a step-by-step algorithm after standard staining, appropriate immunostaining analyses were performed to determine the certainty of diagnosis of FNH, HNF1α-inactivated HCA, inflammatory HCA, β-catenin-activated HCA, or unclassified HCA. The diagnosis of FNH was certain or probable on routine stains in 53% of needle biopsies of group A, whereas after glutamine synthetase staining, the diagnosis was certain in 86.7% as compared with 100% on the corresponding surgical specimen (P=0.04). In needle biopsies of group A, the diagnosis of HCA was certain on routine stains in 58.6% as compared with 94.3% on surgical specimens. After specific immunostaining, diagnosis was established on biopsies with 74.3% certainty, including all HCA subtypes, with similar distribution in surgical specimens. For each "certain diagnosis" paired diagnostic test (biopsy and surgical specimen), a positive correlation was observed (P<0.001). No significant difference was observed between groups A and B for FNH (P=0.714) or for HCA subtypes (P=0.750). Compared with surgical specimens, immunohistochemical analysis performed on biopsies allowed the discrimination of FNH from HCA and the identification of HCA subtypes with good performance.

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Hepatic adenomas: Presumed innocent until proven to be beta-catenin mutated

Cited by 34 publications

References 29 publications

Nucleoporin 62-Like Protein Activates Canonical Wnt Signaling through Facilitating the Nuclear Import of β-Catenin in Zebrafish

Nucleoporin 62-Like Protein Activates Canonical Wnt Signaling through Facilitating the Nuclear Import of β-Catenin in Zebrafish

Microsomal prostaglandin E synthase-1 promotes hepatocarcinogenesis through activation of a novel EGR1/β-catenin signaling axis

Immunohistochemical Markers on Needle Biopsies Are Helpful for the Diagnosis of Focal Nodular Hyperplasia and Hepatocellular Adenoma Subtypes

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