Hepatoblastoma state of the art

Czauderna, Piotr; López‐Terrada, Dolores; Hiyama, Eiso; Häberle, Beate; Malogolowkin, Marcio H.; Meyers, Rebecka L.

doi:10.1097/mop.0000000000000046

Cited by 261 publications

(145 citation statements)

References 59 publications

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“…Timing of transplant can become critical as availability of organs cannot always be planned with the timing of chemotherapy response and recovery from treatment. Early referral for transplant for these select patients is now strongly recommended 7 . Although advances in chemotherapeutics, such as the discovery of cisplatin, have greatly increased survival for some, we must still continue to work to optimize therapies for these children at highest risk 8,9 .…”

Section: Hepatoblastoma: Backgroundmentioning

confidence: 99%

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

Bell

Ranganathan²,

Tao³

et al. 2017

gene expr

104

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Hepatoblastoma is the most common pediatric liver malignancy, typically striking children within the first 3 years of their young lives. While advances in chemotherapy and newer surgical techniques have improved survival in patients with localized disease, unfortunately, for the 25% of patients with metastasis, the overall survival remains poor. These tumors, which are thought to arise from hepatic progenitors or hepatoblasts, hence the name hepatoblastoma, can be categorized by histological subtyping based on their level of cell differentiation. Genomic and histological analysis of human tumor samples has shown exon-3 deletions or missense mutations in gene coding for β-catenin, a downstream effector of the Wnt signaling pathway, in up to 90% of hepatoblastoma cases. The current article will review key aberrations in molecular pathways that are implicated in various subtypes of hepatoblastoma with an emphasis on Wnt signaling. It will also discuss cooperation among components of pathways such as β-catenin and Yes-associated protein in cancer development. Understanding the complex network of molecular signaling in oncogenesis will undoubtedly aid in the discovery of new therapeutics to help combat hepatoblastoma.

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Section: Hepatoblastoma: Backgroundmentioning

confidence: 99%

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

Bell

Ranganathan²,

Tao³

et al. 2017

gene expr

104

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show abstract

“…For example, genetic aberrations in the Wnt signaling pathway are found in a majority of HB cases. Mutations in the β-catenin gene ( CTNNB1 ) [7] and the resulting uncontrolled activation of Wnt signal target gene (Myc, survivin) expression, as well as mutations in telomerase reverse-transcriptase (TERT) promoter regions, promote the development of, and aggressive phenotypes in, HB [8]. In general, oncogenic signaling pathways activate the expression of a set of transcription factors (TFs).…”

Section: Introductionmentioning

confidence: 99%

GATA4 promotes hepatoblastoma cell proliferation by altering expression of miR125b and DKK3

et al. 2016

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GATA4 is a zinc finger DNA-binding protein that plays an important role in mammalian liver development. However, the effects of GATA4 in hepatoblastoma (HB), a common liver cancer in pediatric patients, remain largely unknown. In this study, we demonstrate that GATA4 promotes growth and survival in the Huh6 human hepatoblastoma cell line. GATA4 expression was high in Huh6 cells, and its knockdown decreased expression of Dickkopf-related protein 3 (DKK3), a gene that may contribute to premature or undifferentiated phenotypes in HB. GATA4 also directly bound to the promoter regions of the miRNA miR125b and inhibited its expression in Huh6 cells. DKK3 was a direct target of miR125b in Huh6 cells. Inhibition of miR125b or overexpression of DKK3 promoted proliferation, survival, migration, and invasion in Huh6 cells. This is the first report to demonstrate that GATA4 promotes oncogenesis by inhibiting miR125b-dependent suppression of DKK3 expression. This GATA4/miR125b/DKK3 axis may be a major regulator of growth, migration, invasion, and survival in hepatoma cells, and is therefore a potential therapeutic target or biomarker for progression in HB patients.

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“…Hepatocellular carcinoma (HCC) is the most common type of primary liver tumor in children after hepatoblastoma123. A study using the Surveillance, Epidemiology and End Results (SEER) database examined a cohort of pediatric patients with HCC from 1973 to 2009, and found an overall 5-year survival of 24% and 20-year survival of 8%4.…”

mentioning

confidence: 99%

YAP Subcellular Localization and Hippo Pathway Transcriptome Analysis in Pediatric Hepatocellular Carcinoma

LaQuaglia

Grijalva

Mueller

et al. 2016

Sci Rep

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Pediatric hepatocellular carcinoma (HCC) is a rare tumor which is associated with an extremely high mortality rate due to lack of effective chemotherapy. Recently, the Hippo pathway and its transcriptional co-activator Yes-associated protein (YAP) have been shown to play a role in hepatocyte proliferation and development of HCC in animal models. Therefore, we sought to examine the activity of YAP and the expression of Hippo pathway components in tumor and non-neoplastic liver tissue from 7 pediatric patients with moderately differentiated HCC. None of the patients had underlying cirrhosis or viral hepatitis, which is commonly seen in adults with HCC. This highlights a major difference in the pathogenesis of HCC between children and adults. We found a statistically significant increase in YAP nuclear localization in 100% of tumors. YAP target gene (CCNE1, CTGF, Cyr61) mRNA expression was also increased in the tumors that had the most significant increase in YAP nuclear localization. Based on Ki67 co-localization studies YAP nuclear localization was not simply a marker of proliferation. Our results demonstrate a clear increase in YAP activity in moderately differentiated pediatric HCC, providing evidence that it may play an important role in tumor survival and propagation.

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Hepatoblastoma state of the art

Cited by 261 publications

References 59 publications

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

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

GATA4 promotes hepatoblastoma cell proliferation by altering expression of miR125b and DKK3

YAP Subcellular Localization and Hippo Pathway Transcriptome Analysis in Pediatric Hepatocellular Carcinoma

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