Novel Advances in Understanding of Molecular Pathogenesis of Hepatoblastoma: A Wnt/β-Catenin Perspective

Bell, Danielle; Ranganathan, Sarangarajan; Tao, Junyan; Monga, Satdarshan P.

doi:10.3727/105221616x693639

Cited by 95 publications

(114 citation statements)

References 58 publications

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“…Co-expression of constitutively active β-catenin and constitutively active YAP via SB-HTVI in hepatocytes led to the development of HB in mice, suggesting a role of β-catenin-YAP interaction in the pathogenesis of HB (123) (Figure 6 a ). How these two signaling pathways cooperate in HB development remains under investigation and is also discussed elsewhere (124). An intriguing observation was that, unlike in HB, less than 4% of HCC samples exhibited concomitant activation of β-catenin and YAP, although YAP and β-catenin activation was evident exclusively in a notable subset of HCC cases (123) (Figure 6 a ).…”

Section: Cell Type–specific Roles Of Wnt/β-catenin Signaling In Livermentioning

confidence: 99%

Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology

Russell

Monga

2018

Annu. Rev. Pathol. Mech. Dis.

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346

282

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The liver is an organ that performs a multitude of functions, and its health is pertinent and indispensable to survival. Thus, the cellular and molecular machinery driving hepatic functions is of utmost relevance. The Wnt signaling pathway is one such signaling cascade that enables hepatic homeostasis and contributes to unique hepatic attributes such as metabolic zonation and regeneration. The Wnt/β-catenin pathway plays a role in almost every facet of liver biology. Furthermore, its aberrant activation is also a hallmark of various hepatic pathologies. In addition to its signaling function, β-catenin also plays a role at adherens junctions. Wnt/β-catenin signaling also influences the function of many different cell types. Due to this myriad of functions, Wnt/β-catenin signaling is complex, context-dependent, and highly regulated. In this review, we discuss the Wnt/β-catenin signaling pathway, its role in cell-cell adhesion and liver function, and the cell type–specific roles of Wnt/β-catenin signaling as it relates to liver physiology and pathobiology.

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Section: Cell Type–specific Roles Of Wnt/β-catenin Signaling In Livermentioning

confidence: 99%

Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology

Russell

Monga

2018

Annu. Rev. Pathol. Mech. Dis.

Self Cite

346

282

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“…In the liver, the Wnt pathway is essential for homeostasis, embryogenesis, development, maturation, and regeneration [9]. It is also associated with several pathological conditions such as cirrhosis [10], hepatoblastoma [11,12], and hepatocellular carcinoma (HCC) [13]. Currently, several Wnt molecules with potential pharmacological value are being explored for future therapeutic interventions [14,15].…”

Section: Manuscript To Be Reviewedmentioning

confidence: 99%

Peer Review #2 of "Wnt signaling in liver disease: emerging trends from a bibliometric perspective (v0.2)"

2019

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Background: The Wnt signaling pathway, an evolutionarily conserved molecular transduction cascade, has been identified to play a pivotal role in various physiological and pathological processes of the liver, including homeostasis, regeneration, cirrhosis, and hepatocellular carcinoma. In this study, we aimed to use a bibliometric method to evaluate the emerging trends on Wnt signaling in liver diseases. Methods: Articles were retrieved from the Web of Science Core Collection (WoSCC). We used a bibliometric software, CiteSpace V 5.3.R4, to analyze the active countries or institutions in the research field, the landmark manuscripts, important subtopics, and evolution of scientific ideas. Results: In total, 1,768 manuscripts were published, and each was cited 33.12 times on average. The U.S. published most of the manuscripts, and the most active center was the University of Pittsburgh. The top 5 landmark papers were identified by four bibliometric indexes including citation, burstness, centrality, and usage 2013. The clustering process divided the whole area into 9 research subtopics, and the two major important subtopics were "liver zonation" and "hepatocellular carcinoma". Using the "Partof-Speech" technique, 1,743 terms representing scientific ideas were identified. After 2008, the bursting phrases were "liver development" , "progenitor cells," "hepatic stellate cells", "liver regeneration", "liver fibrosis", "epithelial-mesenchymal transition" and etc. Conclusion: Using bibliometric methods, we quantitatively summarized the advancements and emerging trends in Wnt signaling in liver diseases. These bibliometric findings may pioneer the future direction of this field in the next few years, and further studies are needed.

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“…HBs are believed to originate from hepatic progenitor cells that acquire malignant transformation during embryogenesis. Histologically they show similarity to immature hepatocytes of the developing liver . Most HBs are believed to be of sporadic nature, but about 10–20% have been associated with genetic defects such as Beckwith–Wiedemann syndrome (BWS) or familial adenomatous polyposis (FAP) …”

Section: Introductionmentioning

confidence: 99%

“…The Wnt/β‐catenin signaling pathway is recognized as having a central role in the pathogenesis of HBs . The β‐catenin protein is a key effector of the pathway, affecting cellular decisions such as stem cell maintenance and cell proliferation through modulating the expression of specific target genes.…”

Section: Introductionmentioning

confidence: 99%

A novel tissue‐based ß‐catenin gene and immunohistochemical analysis to exclude familial adenomatous polyposis among children with hepatoblastoma tumors

Dubbink

Hollink

Valente

et al. 2018

Pediatric Blood & Cancer

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Background: The Wnt/ -catenin pathway plays a central role in the pathogenesis of most hepatoblastomas (HBs), that is, up to 60-80% carry activating CTNNB1 mutations. HBs can however also be the first manifestation of familial adenomatous polyposis (FAP). As this is a severe disease, it is important for the patient and related family members to firmly exclude FAP at an early stage.Current diagnosis largely depends on APC germline mutation detection on genomic DNA, which is associated with 10-20% false-negative results. Here, we establish and validate a tissue-basedcatenin gene and immunohistochemical analysis, which complements germline mutation screening to exclude the diagnosis of FAP among HB patients.Methods: Tumor tissues of 18 HB patients, including three FAP cases were subjected to CTNNB1 exon 3 mutational analysis and immunohistochemistry comparing staining patterns for total and exon 3 specific -catenin antibodies.Results: Our novel tissue-based method reliably identified all three FAP patients. Their tumors were characterized by a wild-type exon 3 sequence and a comparable nuclear staining for both antibodies. In contrast, the non-FAP tumors carried missense CTNNB1 mutations combined with a clearly reduced staining for the exon 3 antibody, or complete loss of staining in case of lesions with exon 3 deletions. Conclusion:We have successfully established and validated a novel ß-catenin gene and immunohistochemical diagnostic method, which, when combined with routine germline DNA testing, allows the exclusion of the diagnosis of FAP among HB patients.

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Novel Advances in Understanding of Molecular Pathogenesis of Hepatoblastoma: A Wnt/β-Catenin Perspective

Cited by 95 publications

References 58 publications

Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology

Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology

Peer Review #2 of "Wnt signaling in liver disease: emerging trends from a bibliometric perspective (v0.2)"

A novel tissue‐based ß‐catenin gene and immunohistochemical analysis to exclude familial adenomatous polyposis among children with hepatoblastoma tumors

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