{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T03:53:20Z","timestamp":1772942000942,"version":"3.50.1"},"reference-count":93,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T00:00:00Z","timestamp":1568937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hepatoblastoma (HB) is the most common form of primary liver malignancy found in pediatric populations. HB is considered to be clonal and arises from hepatoblasts, or embryonic liver progenitor cells. These less differentiated tumor-initiating progenitor cells, or cancer stem cells (CSCs), may contribute to tumor recurrence and resistance to therapies, and have high metastatic abilities. Phenotypic heterogeneity, undesired genetic and epigenetic alterations, and dysregulated signaling pathways provide CSCs with a survival advantage over current therapies. The molecular and cellular basis of HB and the mechanism of CSC induction are not fully understood. The Wnt\/beta-catenin pathway is one of the major developmental pathways and is believed to play an important role in the pathogenesis of HB and CSC formation. This review summarizes the cellular and molecular characteristics of HB with a specific emphasis on CSCs and Wnt\/beta-catenin signaling.<\/jats:p>","DOI":"10.3390\/cancers11101406","type":"journal-article","created":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T10:48:14Z","timestamp":1568976494000},"page":"1406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["The Emerging Roles of Cancer Stem Cells and Wnt\/Beta-Catenin Signaling in Hepatoblastoma"],"prefix":"10.3390","volume":"11","author":[{"given":"Nirmala","family":"Mavila","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"},{"name":"Department of Biomedical Sciences, Division of Applied Cell Biology and Physiology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyothi","family":"Thundimadathil","sequence":"additional","affiliation":[{"name":"Division of Research and Development, Bachem Americas, Inc., Torrance, CA 90505, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/MOP.0000000000000046","article-title":"Hepatoblastoma state of the art: Pathology, genetics, risk stratification, and chemotherapy","volume":"26","author":"Czauderna","year":"2014","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3727\/105221616X693639","article-title":"Novel advances in understanding of molecular pathogenesis of hepatoblastoma: A Wnt\/Beta-catenin perspective","volume":"17","author":"Bell","year":"2017","journal-title":"Gene Expr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1002\/cncr.23169","article-title":"Trends in childhood cancer incidence in the U.S. (1992\u20132004)","volume":"112","author":"Linabery","year":"2008","journal-title":"Cancer"},{"key":"ref_4","first-page":"3032","article-title":"Increased risk of hepatoblastoma among immature children with a lower birth weight","volume":"58","author":"Tanimura","year":"1998","journal-title":"Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0022-3476(97)70239-7","article-title":"Association between hepatoblastoma and very low birth weight: A trend or a chance?","volume":"130","author":"Ikeda","year":"1997","journal-title":"J. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1093\/aje\/kwj104","article-title":"Maternal and infant birth characteristics and hepatoblastoma","volume":"163","author":"McLaughlin","year":"2006","journal-title":"Am. J. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/pbc.20115","article-title":"Hepatoblastoma in a girl with biliary atresia: Coincidence or co-incidence","volume":"43","author":"Taat","year":"2004","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/j.jpedsurg.2004.05.020","article-title":"Hepatoblastoma\u2014Evolution of management and outcome and significance of histology of the resected tumor. A 31-year experience with 40 cases","volume":"39","author":"Davies","year":"2004","journal-title":"J. Pediatr. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1002\/1097-0142(19890901)64:5<1082::AID-CNCR2820640520>3.0.CO;2-G","article-title":"Histopathology and prognosis in childhood hepatoblastoma and hepatocarcinoma","volume":"64","author":"Haas","year":"1989","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ejca.2015.09.023","article-title":"The Children\u2019s Hepatic Tumors International Collaboration (Chic): Novel global rare tumor database yields new prognostic factors in hepatoblastoma and becomes a research model","volume":"52","author":"Czauderna","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1002\/hep.21328","article-title":"Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas","volume":"44","author":"Luo","year":"2006","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1093\/carcin\/bgx050","article-title":"Fxr-Gankyrin axis is involved in development of pediatric liver cancer","volume":"38","author":"Valanejad","year":"2017","journal-title":"Carcinogenesis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ccr.2008.11.002","article-title":"Hepatic stem-like phenotype and interplay of Wnt\/Beta-catenin and Myc signaling in aggressive childhood liver cancer","volume":"14","author":"Cairo","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/j.jhep.2014.08.009","article-title":"The genomic landscape of hepatoblastoma and their progenies with Hcc-like features","volume":"61","author":"Trippel","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.humpath.2017.10.007","article-title":"General paucity of genomic alteration and low tumor mutation burden in refractory and metastatic hepatoblastoma: Comprehensive genomic profiling study","volume":"70","author":"Lee","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/modpathol.3800977","article-title":"Sporadic childhood hepatoblastomas show activation of beta-catenin, mismatch repair defects and p53 Mutations","volume":"21","author":"Curia","year":"2008","journal-title":"Mod. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1007\/s003830000576","article-title":"High frequency of beta-catenin mutations in hepatoblastoma","volume":"17","author":"Udatsu","year":"2001","journal-title":"Pediatr. Surg. Int."},{"key":"ref_18","first-page":"901","article-title":"Frequent deletions and mutations of the beta-catenin gene are associated with overexpression of cyclin D1 and fibronectin and poorly differentiated histology in childhood hepatoblastoma","volume":"7","author":"Takayasu","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_19","first-page":"269","article-title":"Childhood hepatoblastomas frequently carry a mutated degradation targeting box of the beta-catenin gene","volume":"59","author":"Koch","year":"1999","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/(SICI)1098-2264(199908)25:4<399::AID-GCC14>3.0.CO;2-X","article-title":"Beta-catenin accumulation and mutation of the CTNNB1 gene in hepatoblastoma","volume":"25","author":"Hofmann","year":"1999","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0002-9440(10)64567-1","article-title":"Characterization of genomic alterations in hepatoblastomas. A role for gains on chromosomes 8q and 20 as predictors of poor outcome","volume":"157","author":"Weber","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH804>3.0.CO;2-R","article-title":"Nuclear localization of beta-catenin is an important prognostic factor in hepatoblastoma","volume":"193","author":"Park","year":"2001","journal-title":"J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.15252\/emmm.201707814","article-title":"Mutant CTNNB1 and histological heterogeneity define metabolic subtypes of hepatoblastoma","volume":"9","author":"Crippa","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e88549","DOI":"10.1172\/jci.insight.88549","article-title":"Hepatoblastoma modeling in mice places Nrf2 within a cancer field established by mutant beta-catenin","volume":"1","author":"Comerford","year":"2016","journal-title":"JCI Insight"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1083\/jcb.200803147","article-title":"Caprin-2 enhances canonical Wnt signaling through regulating Lrp5\/6 phosphorylation","volume":"182","author":"Ding","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1002\/hep.27243","article-title":"Exome sequencing of hepatoblastoma reveals novel mutations and cancer genes in the Wnt pathway and ubiquitin ligase complex","volume":"60","author":"Jia","year":"2014","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1002\/hep.29677","article-title":"C\/Ebpalpha-dependent preneoplastic tumor foci are the origin of hepatocellular carcinoma and aggressive pediatric liver cancer","volume":"67","author":"Cast","year":"2018","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/mpo.10175","article-title":"Stem-like cells in hepatoblastoma","volume":"39","author":"Ruck","year":"2002","journal-title":"Med. Pediatr. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5108653","DOI":"10.1155\/2017\/5108653","article-title":"The recent advances on liver cancer stem cells: Biomarkers, separation, and therapy","volume":"2017","author":"Xiao","year":"2017","journal-title":"Anal. Cell Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.trsl.2014.07.009","article-title":"Aberrant expression of cancer stem cell markers (Cd44, Cd90, and Cd133) contributes to disease progression and reduced survival in hepatoblastoma patients: 4-year survival data","volume":"165","author":"Bahnassy","year":"2015","journal-title":"Transl. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.stem.2010.11.010","article-title":"Mir-130b promotes Cd133+ liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1","volume":"7","author":"Ma","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.yexcr.2012.09.007","article-title":"Biology and clinical implications of Cd133+ liver cancer stem cells","volume":"319","author":"Ma","year":"2013","journal-title":"Exp. Cell Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1002\/hep.22141","article-title":"Expansion of liver cancer stem cells during aging in methionine adenosyltransferase 1A-deficient mice","volume":"47","author":"Rountree","year":"2008","journal-title":"Hepatology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1634\/stemcells.2008-0332","article-title":"Expansion of Cd133-expressing liver cancer stem cells in liver-specific phosphatase and tensin homolog deleted on chromosome 10-deleted mice","volume":"27","author":"Rountree","year":"2009","journal-title":"Stem Cells"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Mavila, N., James, D., Utley, S., Cu, N., Coblens, O., Mak, K., Wang, K.S., Rountree, B., and Kahn, M. (2012). Fibroblast growth factor receptor-mediated activation of akt-beta-catenin-cbp pathway regulates survival and proliferation of murine hepatoblasts and hepatic tumor initiating stem cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050401"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1002\/hep.27203","article-title":"Expansion of prominin-1-expressing cells in association with fibrosis of biliary atresia","volume":"60","author":"Mavila","year":"2014","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1097\/MEG.0b013e32836019d8","article-title":"Relevant markers of cancer stem cells indicate a poor prognosis in hepatocellular carcinoma patients: A meta-analysis","volume":"25","author":"Ma","year":"2013","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/hep.24739","article-title":"Cd133+ Liver tumor-initiating cells promote tumor angiogenesis, growth, and self-renewal through neurotensin\/interleukin-8\/Cxcl1 signaling","volume":"55","author":"Tang","year":"2012","journal-title":"Hepatology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12964-018-0222-5","article-title":"Inhibition of CREB binding protein-beta-catenin signaling down regulates Cd133 expression and activates PP2A-PTEN signaling in tumor initiating liver cancer cells","volume":"16","author":"Tang","year":"2018","journal-title":"Cell Commun. Signal."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1038\/sj.onc.1210811","article-title":"Cd133+ HCC Cancer stem cells confer chemoresistance by preferential expression of the Akt\/PKB survival pathway","volume":"27","author":"Ma","year":"2008","journal-title":"Oncogene"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.tranon.2018.10.008","article-title":"Targeting Pim Kinases Affects Maintenance of Cd133 Tumor Cell Population in Hepatoblastoma","volume":"12","author":"Stafman","year":"2019","journal-title":"Transl. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10831","DOI":"10.1158\/0008-5472.CAN-07-0908","article-title":"Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma","volume":"67","author":"Yamashita","year":"2007","journal-title":"Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/hep.24122","article-title":"Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stem\/progenitor cells in humans","volume":"53","author":"Yoon","year":"2011","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"G233","DOI":"10.1152\/ajpgi.00069.2014","article-title":"EpCAM and the biology of hepatic stem\/progenitor cells","volume":"308","author":"Theise","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.mod.2009.06.939","article-title":"Mouse hepatoblasts at distinct developmental stages are characterized by expression of EpCAM and DLK1: Drastic change of EpCAM expression during liver development","volume":"126","author":"Tanaka","year":"2009","journal-title":"Mech. Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/ncb1824","article-title":"Nuclear signalling by tumour-associated antigen EpCAM","volume":"11","author":"Maetzel","year":"2009","journal-title":"Nat. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1158\/0008-5472.CAN-07-6013","article-title":"EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma","volume":"68","author":"Yamashita","year":"2008","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1475-2867-10-44","article-title":"Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies","volume":"10","author":"Murr","year":"2010","journal-title":"Cancer Cell Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ccr.2008.01.013","article-title":"Significance of CD90+ cancer stem cells in human liver cancer","volume":"13","author":"Yang","year":"2008","journal-title":"Cancer Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4741","DOI":"10.1038\/onc.2010.215","article-title":"Cancer stem cells and drug resistance: An emerging axis of evil in the war on cancer","volume":"29","author":"Singh","year":"2010","journal-title":"Oncogene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.cell.2008.03.027","article-title":"The epithelial-mesenchymal transition generates cells with properties of stem cells","volume":"133","author":"Mani","year":"2008","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.4161\/cc.7.23.7049","article-title":"Early origin of cancer metastases: Dissemination and evolution of premalignant cells","volume":"7","author":"Ansieau","year":"2008","journal-title":"Cell Cycle"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"89","DOI":"10.20892\/j.issn.2095-3941.2018.0077","article-title":"Periostin mediates epithelial-mesenchymal transition through the MAPK\/ERK pathway in hepatoblastoma","volume":"16","author":"Chen","year":"2019","journal-title":"Cancer Biol. Med."},{"key":"ref_54","first-page":"2427","article-title":"Dram1 regulates the migration and invasion of hepatoblastoma cells via autophagy-EMT pathway","volume":"16","author":"Chen","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.biopha.2018.02.026","article-title":"Kockdown of Oip5-As1 Expression Inhibits Proliferation, Metastasis and Emt Progress in Hepatoblastoma Cells through up-Regulating Mir-186a-5p and Down-Regulating Zeb1","volume":"101","author":"Zhang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3892\/mmr.2015.3359","article-title":"Thymosin beta 4 promotes hepatoblastoma metastasis via the induction of epithelial-mesenchymal transition","volume":"12","author":"Fu","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1053\/j.gastro.2015.02.056","article-title":"Beta-catenin signaling and roles in liver homeostasis, injury, and tumorigenesis","volume":"148","author":"Monga","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1146\/annurev-pathol-020117-044010","article-title":"Wnt\/Beta-catenin signaling in liver development, homeostasis, and pathobiology","volume":"13","author":"Russell","year":"2018","journal-title":"Annu. Rev. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S1097-2765(03)00484-2","article-title":"Mechanism for Wnt coreceptor activation","volume":"13","author":"Tamai","year":"2004","journal-title":"Mol. Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.devcel.2009.06.016","article-title":"Wnt\/Beta-catenin signaling: Components, mechanisms, and diseases","volume":"17","author":"MacDonald","year":"2009","journal-title":"Dev. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/35035117","article-title":"Ldl-receptor-related proteins in wnt signal transduction","volume":"407","author":"Tamai","year":"2000","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3797","DOI":"10.1093\/emboj\/16.13.3797","article-title":"Beta-catenin is a target for the ubiquitin-proteasome pathway","volume":"16","author":"Aberle","year":"1997","journal-title":"EMBO J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1756-9966-30-96","article-title":"Hgf\/C-Met related activation of beta-catenin in hepatoblastoma","volume":"30","author":"Purcell","year":"2011","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1002\/path.1662","article-title":"Mutations and elevated transcriptional activity of conductin (AXIN2) in hepatoblastomas","volume":"204","author":"Koch","year":"2004","journal-title":"J. Pathol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"668","DOI":"10.3389\/fgene.2018.00668","article-title":"Whole-Genome Sequencing Identifies a Novel Variation of Was Gene Coordinating with Heterozygous Germline Mutation of Apc to Enhance Hepatoblastoma Oncogenesis","volume":"9","author":"Zhang","year":"2018","journal-title":"Front. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1053\/j.gastro.2014.05.004","article-title":"Activation of beta-catenin and yap1 in human hepatoblastoma and induction of hepatocarcinogenesis in mice","volume":"3","author":"Tao","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1101\/gad.1909210","article-title":"The Hippo-YAP pathway in organ size control and tumorigenesis: An updated version","volume":"24","author":"Zhao","year":"2010","journal-title":"Genes Dev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s42003-018-0077-8","article-title":"PARP1 activation increases expression of modified tumor suppressors and pathways underlying development of aggressive hepatoblastoma","volume":"1","author":"Valanejad","year":"2018","journal-title":"Commun. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3882","DOI":"10.1038\/s41467-019-11533-x","article-title":"Greb1 induced by Wnt signaling promotes development of hepatoblastoma by suppressing TGFbeta signaling","volume":"10","author":"Matsumoto","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1002\/pbc.20698","article-title":"Should children at risk for familial adenomatous polyposis be screened for hepatoblastoma and children with apparently sporadic hepatoblastoma be screened for APC germline mutations?","volume":"47","author":"Aretz","year":"2006","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4515","DOI":"10.1158\/0008-5472.CAN-13-3275","article-title":"Beta-catenin activation in a novel liver progenitor cell type is sufficient to cause hepatocellular carcinoma and hepatoblastoma","volume":"74","author":"Mokkapati","year":"2014","journal-title":"Cancer Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.1158\/0008-5472.CAN-07-6691","article-title":"Wnt\/Beta-catenin signaling contributes to activation of normal and tumorigenic liver progenitor cells","volume":"68","author":"Yang","year":"2008","journal-title":"Cancer Res."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Crist\u00f3bal, I., Sanz-\u00c1lvarez, M., Luque, M., Caram\u00e9s, C., Rojo, F., and Garc\u00eda-Foncillas, J. (2019). The Role of Micrornas in Hepatoblastoma Tumors. Cancers, 11.","DOI":"10.3390\/cancers11030409"},{"key":"ref_74","first-page":"1126","article-title":"MicroRNA regulation of liver cancer stem cells","volume":"8","author":"Lou","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"20471","DOI":"10.1073\/pnas.1009009107","article-title":"Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer","volume":"107","author":"Cairo","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/hep4.1029","article-title":"MicroRNA therapy inhibits hepatoblastoma growth in vivo by targeting beta-catenin and Wnt signaling","volume":"1","author":"Indersie","year":"2017","journal-title":"Hepatol. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1010428317716076","DOI":"10.1177\/1010428317716076","article-title":"Let7b Modulates the Wnt\/Beta-catenin pathway in liver cancer cells via downregulated Frizzled4","volume":"39","author":"Cai","year":"2017","journal-title":"Tumour Biol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Jin, B., Wang, W., Meng, X.X., Du, G., Li, J., Zhang, S.Z., Fu, Z.H., and Zhou, B.H. (2016). Let-7 inhibits self-renewal of hepatocellular cancer stem-like cells through regulating the epithelial-mesenchymal transition and the Wnt signaling pathway. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2904-y"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1002\/hep.28821","article-title":"Octamer 4\/microRNA-1246 signaling axis drives Wnt\/beta-catenin activation in liver cancer stem cells","volume":"64","author":"Chai","year":"2016","journal-title":"Hepatology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.3892\/or.2017.5924","article-title":"miR-217 targeting DKK1 promotes cancer stem cell properties via activation of the Wnt signaling pathway in hepatocellular carcinoma","volume":"38","author":"Jiang","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.bbrc.2014.03.135","article-title":"miR-612 suppresses the stemness of liver cancer via Wnt\/Beta-catenin signaling","volume":"447","author":"Tang","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"36995","DOI":"10.1074\/jbc.M110.133744","article-title":"miR-200a regulates epithelial-mesenchymal to stem-like transition via ZEB2 and beta-catenin signaling","volume":"285","author":"Xia","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Del Vecchio, C.A., Feng, Y., Sokol, E.S., Tillman, E.J., Sanduja, S., Reinhardt, F., and Gupta, P.B. (2014). De-differentiation confers multidrug resistance via noncanonical PERK-Nrf2 signaling. PLoS Biol., 12.","DOI":"10.1371\/journal.pbio.1001945"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.stem.2018.11.011","article-title":"Phenotypic plasticity: Driver of cancer initiation, progression, and therapy resistance","volume":"24","author":"Gupta","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1111\/cas.12471","article-title":"Safely targeting cancer stem cells via selective catenin coactivator antagonism","volume":"105","author":"Lenz","year":"2014","journal-title":"Cancer Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/j.ajpath.2014.04.002","article-title":"Identification and characterization of a novel small-molecule inhibitor of beta-catenin signaling","volume":"184","author":"Delgado","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/S1359-6446(05)03613-5","article-title":"Investigating Wnt signaling: A chemogenomic safari","volume":"10","author":"McMillan","year":"2005","journal-title":"Drug Discov. Today"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"12682","DOI":"10.1073\/pnas.0404875101","article-title":"A small molecule inhibitor of beta-catenin\/creb-binding protein transcription [Corrected]","volume":"101","author":"Emami","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"467","DOI":"10.2174\/1573406054864098","article-title":"Icg-001, a Novel Small Molecule Regulator of Tcf\/Beta-Catenin Transcription","volume":"1","author":"Eguchi","year":"2005","journal-title":"Med. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1158\/1535-7163.MCT-07-2063","article-title":"A small-molecule inhibitor of Tcf\/beta-catenin signaling down-regulates Ppargamma and Ppardelta Activities","volume":"7","author":"Handeli","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S1535-6108(03)00334-9","article-title":"Small-molecule antagonists of the oncogenic Tcf\/beta-catenin protein complex","volume":"5","author":"Lepourcelet","year":"2004","journal-title":"Cancer Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2426","DOI":"10.1002\/ijc.24810","article-title":"Small molecule antagonists of Tcf4\/Beta-catenin complex inhibit the growth of HCC cells in vitro and in vivo","volume":"126","author":"Wei","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.18632\/oncotarget.26668","article-title":"mTOR inhibition affects Yap1-Beta-catenin-induced hepatoblastoma growth and development","volume":"10","author":"Molina","year":"2019","journal-title":"Oncotarget"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/10\/1406\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:22:19Z","timestamp":1760188939000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/10\/1406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,20]]},"references-count":93,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["cancers11101406"],"URL":"https:\/\/doi.org\/10.3390\/cancers11101406","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,20]]}}}