{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:41:48Z","timestamp":1790379708546,"version":"4.1.0"},"reference-count":146,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T00:00:00Z","timestamp":1562025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670425"],"award-info":[{"award-number":["81670425"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"\u2018\u2018Double First Class\u2019\u2019 University Project of China Pharmaceutical University","award":["CPU2018GF04"],"award-info":[{"award-number":["CPU2018GF04"]}]},{"name":"Open Project of State Key Laboratory of Natural Medicines of China Pharmaceutical University","award":["3144060173"],"award-info":[{"award-number":["3144060173"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["3011900173"],"award-info":[{"award-number":["3011900173"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Liver cancer is among the leading global healthcare issues associated with high morbidity and mortality. Liver cancer consists of hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), hepatoblastoma (HB), and several other rare tumors. Progression has been witnessed in understanding the interactions between etiological as well as environmental factors and the host in the development of liver cancers. However, the pathogenesis remains poorly understood, hampering the design of rational strategies aiding in preventing liver cancers. Accumulating evidence demonstrates that aberrant activation of the Wnt\/\u03b2-catenin signaling pathway plays an important role in the initiation and progression of HCC, CCA, and HB. Targeting Wnt\/\u03b2-catenin signaling potentiates a novel avenue for liver cancer treatment, which may benefit from the development of numerous small-molecule inhibitors and biologic agents in this field. In this review, we discuss the interaction between various etiological factors and components of Wnt\/\u03b2-catenin signaling early in the precancerous lesion and the acquired mechanisms to further enhance Wnt\/\u03b2-catenin signaling to promote robust cancer formation at later stages. Additionally, we shed light on current relevant inhibitors tested in liver cancers and provide future perspectives for preclinical and clinical liver cancer studies.<\/jats:p>","DOI":"10.3390\/cancers11070926","type":"journal-article","created":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T12:11:17Z","timestamp":1562069477000},"page":"926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":123,"title":["Wnt\/\u03b2-Catenin Signaling in Liver Cancers"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0088-8778","authenticated-orcid":false,"given":"Wenhui","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6798-3206","authenticated-orcid":false,"given":"Ron","family":"Smits","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center and Postgraduate School Molecular Medicine, Rotterdam 3015 CN, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiping","family":"Hao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyong","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacology, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nrc1934","article-title":"Hepatocellular carcinoma pathogenesis: From genes to environment","volume":"6","author":"Farazi","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1016\/S0140-6736(13)61903-0","article-title":"Cholangiocarcinoma","volume":"383","author":"Razumilava","year":"2014","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1053\/jhep.2003.50375","article-title":"Epidemiology of primary hepatic malignancies in U.S. children","volume":"38","author":"Darbari","year":"2003","journal-title":"Hepatology"},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.3892\/ol.2014.1828","article-title":"Wnt\/\u03b2-catenin signaling pathway may regulate the expression of angiogenic growth factors in hepatocellular carcinoma","volume":"7","author":"Qu","year":"2014","journal-title":"Oncol. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc3419","article-title":"WNT signalling pathways as therapeutic targets in cancer","volume":"13","author":"Anastas","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nrc2389","article-title":"Wnt signalling and its impact on development and cancer","volume":"8","author":"Klaus","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00535-016-1299-5","article-title":"Action and function of Wnt\/beta-catenin signaling in the progression from chronic hepatitis C to hepatocellular carcinoma","volume":"52","author":"Wang","year":"2017","journal-title":"J. Gastroenterol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1126\/science.287.5458.1606","article-title":"Wnt signaling in oncogenesis and embryogenesis\u2014A look outside the nucleus","volume":"287","author":"Peifer","year":"2000","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.clinre.2011.05.010","article-title":"The Wnt\/beta-catenin pathway as a therapeutic target in human hepatocellular carcinoma","volume":"35","author":"Dahmani","year":"2011","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4228","DOI":"10.2337\/db12-1710","article-title":"Antiangiogenic and antineuroinflammatory effects of kallistatin through interactions with the canonical Wnt pathway","volume":"62","author":"Liu","year":"2013","journal-title":"Diabetes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0960-9822(99)80091-8","article-title":"The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell","volume":"9","author":"Hart","year":"1999","journal-title":"Curr. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1177\/0192623315621192","article-title":"Tankyrase Inhibition Causes Reversible Intestinal Toxicity in Mice with a Therapeutic Index <1","volume":"44","author":"Zhong","year":"2016","journal-title":"Toxicol. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4611","DOI":"10.1111\/bph.14038","article-title":"Regulation of Wnt\/beta-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding","volume":"174","author":"Mariotti","year":"2017","journal-title":"Br. J. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tian, Y., Mok, M.T., Yang, P., and Cheng, A.S. (2016). Epigenetic Activation of Wnt\/beta-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis. Cancers (Basel), 8.","DOI":"10.3390\/cancers8080076"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1074\/jbc.M111.299099","article-title":"Specific armadillo repeat sequences facilitate beta-catenin nuclear transport in live cells via direct binding to nucleoporins Nup62, Nup153, and RanBP2\/Nup358","volume":"287","author":"Sharma","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_17","first-page":"49","article-title":"WNT\/\u03b2-catenin pathway activation in hepatocellular carcinoma: A clinical perspective","volume":"4","author":"Ma","year":"2014","journal-title":"Gastrointest. Cancer Targets Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.ccr.2014.01.030","article-title":"Viral-human chimeric transcript predisposes risk to liver cancer development and progression","volume":"25","author":"Lau","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/317489a0","article-title":"The hepatitis B virus","volume":"317","author":"Tiollais","year":"1985","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/ijc.28697","article-title":"Epigenetic silencing of SFRP1 and SFRP5 by hepatitis B virus X protein enhances hepatoma cell tumorigenicity through Wnt signaling pathway","volume":"135","author":"Xie","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.canlet.2010.09.018","article-title":"Hepatitis B viral X protein interacts with tumor suppressor adenomatous polyposis coli to activate Wnt\/beta-catenin signaling","volume":"300","author":"Hsieh","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1002\/hep.20245","article-title":"Hepatitis B virus X protein is essential for the activation of Wnt\/beta-catenin signaling in hepatoma cells","volume":"39","author":"Cha","year":"2004","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1136\/gutjnl-2013-305584","article-title":"Cell cycle-related kinase mediates viral-host signalling to promote hepatitis B virus-associated hepatocarcinogenesis","volume":"63","author":"Yu","year":"2014","journal-title":"Gut"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2937","DOI":"10.1007\/s00705-017-3462-6","article-title":"Modulation of Wnt signaling pathway by hepatitis B virus","volume":"162","author":"Daud","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2966","DOI":"10.1099\/vir.0.83108-0","article-title":"Gene-expression profiles of a hepatitis B small surface antigen-secreting cell line reveal upregulation of lymphoid enhancer-binding factor 1","volume":"88","author":"Tian","year":"2007","journal-title":"J. Gen. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/1756-9966-28-58","article-title":"Role of hepatitis B surface antigen in the development of hepatocellular carcinoma: Regulation of lymphoid enhancer-binding factor 1","volume":"28","author":"Tian","year":"2009","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ccr.2014.02.011","article-title":"RNA identity crisis: Hepatitis B walks the LINE","volume":"25","author":"Niknafs","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Budzinska, M.A., Shackel, N.A., Urban, S., and Tu, T. (2018). Cellular Genomic Sites of Hepatitis B Virus DNA Integration. Genes (Basel), 9.","DOI":"10.3390\/genes9070365"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1136\/gutjnl-2014-308482","article-title":"Authors\u2019 response: Virus-host interactions in HBV-related hepatocellular carcinoma: More to be revealed?","volume":"64","author":"Cao","year":"2015","journal-title":"Gut"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1146\/annurev-pathol-012414-040323","article-title":"Hepatitis C virus-associated cancer","volume":"10","author":"Lin","year":"2015","journal-title":"Annu. Rev. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1046\/j.1365-2893.2000.00201.x","article-title":"Properties of the hepatitis C virus core protein: A structural protein that modulates cellular processes","volume":"7","author":"McLauchlan","year":"2000","journal-title":"J. Viral. Hepat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1574-6968.2001.tb10796.x","article-title":"Hepatitis C virus core protein: Intriguing properties and functional relevance","volume":"202","author":"Ray","year":"2001","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1002\/hep.20668","article-title":"Hepatitis C virus core protein stimulates hepatocyte growth: Correlation with upregulation of wnt-1 expression","volume":"41","author":"Fukutomi","year":"2005","journal-title":"Hepatology"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Liu, J., Ding, X., Tang, J., Cao, Y., Hu, P., Zhou, F., Shan, X., Cai, X., Chen, Q., and Ling, N. (2011). Enhancement of canonical Wnt\/\u03b2-catenin signaling activity by HCV core protein promotes cell growth of hepatocellular carcinoma cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027496"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1743-422X-11-117","article-title":"Promoter hypermethylation of Wnt pathway inhibitors in hepatitis C virus-induced multistep hepatocarcinogenesis","volume":"11","author":"Umer","year":"2014","journal-title":"Virol. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.1038\/onc.2013.225","article-title":"Hepatitis C virus core protein epigenetically silences SFRP1 and enhances HCC aggressiveness by inducing epithelial\u2014mesenchymal transition","volume":"33","author":"Quan","year":"2014","journal-title":"Oncogene"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.virusres.2011.05.014","article-title":"Hypermethylated levels of E-cadherin promoter in Huh-7 cells expressing the HCV core protein","volume":"160","author":"Ripoli","year":"2011","journal-title":"Virus Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ccr.2011.01.040","article-title":"Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by Oncogenomic screening","volume":"19","author":"Sawey","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.jhep.2009.06.026","article-title":"Nonstructural 5A protein activates beta-catenin signaling cascades: Implication of hepatitis C virus-induced liver pathogenesis","volume":"51","author":"Park","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12232","DOI":"10.1074\/jbc.M312245200","article-title":"The Hepatitis C virus NS5A protein activates a phosphoinositide 3-kinase-dependent survival signaling cascade","volume":"279","author":"Street","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1099\/vir.0.80204-0","article-title":"Hepatitis C virus NS5A: Tales of a promiscuous protein","volume":"85","author":"Macdonald","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5006","DOI":"10.1128\/JVI.79.8.5006-5016.2005","article-title":"Hepatitis C virus NS5A-mediated activation of phosphoinositide 3-kinase results in stabilization of cellular \u03b2-catenin and stimulation of \u03b2-catenin-responsive transcription","volume":"79","author":"Street","year":"2005","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"35755","DOI":"10.1074\/jbc.M302889200","article-title":"Hepatitis C virus and HIV envelope proteins collaboratively mediate interleukin-8 secretion through activation of p38 MAP kinase and SHP2 in hepatocytes","volume":"278","author":"Balasubramanian","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molcel.2011.05.014","article-title":"SHP2 tyrosine phosphatase converts parafibromin\/Cdc73 from a tumor suppressor to an oncogenic driver","volume":"43","author":"Takahashi","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1002\/hep.25849","article-title":"Hepatitis C virus-induced up-regulation of microRNA-155 promotes hepatocarcinogenesis by activating Wnt signaling","volume":"56","author":"Zhang","year":"2012","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.ydbio.2003.12.024","article-title":"The presence of FGF2 signaling determines whether \u03b2-catenin exerts effects on proliferation or neuronal differentiation of neural stem cells","volume":"268","author":"Israsena","year":"2004","journal-title":"Dev. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1099\/vir.0.000145","article-title":"The hepatitis C virus NS5A protein blocks EGFR degradation via a proline motif dependent interaction","volume":"96","author":"Igloi","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/sj.embor.embor735","article-title":"Wnt1 and Wnt5a induce cyclin D1 expression through ErbB1 transactivation in HC11 mammary epithelial cells","volume":"4","author":"Civenni","year":"2003","journal-title":"EMBO Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9012","DOI":"10.1038\/srep09012","article-title":"Interferon-\u03b1 inducible protein 6 impairs EGFR activation by CD81 and inhibits hepatitis C virus infection","volume":"5","author":"Meyer","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10935","DOI":"10.1128\/JVI.00750-12","article-title":"Hepatitis C virus induces epidermal growth factor receptor activation via CD81 binding for viral internalization and entry","volume":"86","author":"Diao","year":"2012","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.4161\/cbt.5.9.3151","article-title":"Review Cross-talk of WNT and FGF Signaling Pathways at GSK3\u03b2 to Regulate \u03b2-Catenin and SNAIL Signaling Cascades","volume":"5","author":"Katoh","year":"2006","journal-title":"Cancer Biol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1136\/gutjnl-2014-308003","article-title":"Modulation of HCV reinfection after orthotopic liver transplantation by fibroblast growth factor-2 and other non-interferon mediators","volume":"65","author":"Van","year":"2015","journal-title":"Gut"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jhep.2015.02.030","article-title":"Restoration of Wnt\/beta-catenin signaling attenuates alcoholic liver disease progression in a rat model","volume":"63","author":"Huang","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/acer.12727","article-title":"Chronic Ethanol-Induced Impairment of Wnt\/beta-Catenin Signaling is Attenuated by PPAR-delta Agonist","volume":"39","author":"Xu","year":"2015","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"186","DOI":"10.2174\/1874467208666150817111256","article-title":"Role of the Wnt\/beta-Catenin Pathway in the Pathogenesis of Alcoholic Liver Disease","volume":"10","author":"Behari","year":"2017","journal-title":"Curr. Mol. Pharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1002\/hep.24766","article-title":"Beta-catenin is essential for ethanol metabolism and protection against alcohol-mediated liver steatosis in mice","volume":"55","author":"Liu","year":"2012","journal-title":"Hepatology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1053\/j.gastro.2012.05.048","article-title":"Beta-Catenin regulates hepatic mitochondrial function and energy balance in mice","volume":"143","author":"Lehwald","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-3-319-09614-8_11","article-title":"Alcohol consumption, Wnt\/beta-catenin signaling, and hepatocarcinogenesis","volume":"815","author":"Mercer","year":"2015","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1053\/j.gastro.2017.01.021","article-title":"Stearoyl-CoA Desaturase Promotes Liver Fibrosis and Tumor Development in Mice via a Wnt Positive-Signaling Loop by Stabilization of Low-Density Lipoprotein-Receptor-Related Proteins 5 and 6","volume":"152","author":"Lai","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1002\/hep.24491","article-title":"The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: An international collaborative study","volume":"54","author":"Bhala","year":"2011","journal-title":"Hepatology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/nrrheum.2009.137","article-title":"Wnt and PPARgamma signaling in osteoblastogenesis and adipogenesis","volume":"5","author":"Takada","year":"2009","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1126\/science.289.5481.950","article-title":"Inhibition of adipogenesis by Wnt signaling","volume":"289","author":"Ross","year":"2000","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.cmet.2013.11.023","article-title":"The combined hyperlipidemia caused by impaired Wnt-LRP6 signaling is reversed by Wnt3a rescue","volume":"19","author":"Go","year":"2014","journal-title":"Cell Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4453","DOI":"10.3390\/nu7064453","article-title":"Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) Is a Novel Nutritional Therapeutic Target for Hyperlipidemia, Non-Alcoholic Fatty Liver Disease, and Atherosclerosis","volume":"7","author":"Go","year":"2015","journal-title":"Nutrients"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1096\/fj.15-271171","article-title":"Nonalcoholic fatty liver disease induced by noncanonical Wnt and its rescue by Wnt3a","volume":"29","author":"Wang","year":"2015","journal-title":"FASEB J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1172\/JCI92863","article-title":"Aortic carboxypeptidase-like protein, a WNT ligand, exacerbates nonalcoholic steatohepatitis","volume":"128","author":"Teratani","year":"2018","journal-title":"J. Clin. Invest."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6020","DOI":"10.1038\/onc.2017.207","article-title":"Wnt\/beta-catenin activation and macrophage induction during liver cancer development following steatosis","volume":"36","author":"Debebe","year":"2017","journal-title":"Oncogene"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4803","DOI":"10.1158\/0008-5472.CAN-14-3786","article-title":"Histone Deacetylase HDAC8 Promotes Insulin Resistance and beta-Catenin Activation in NAFLD-Associated Hepatocellular Carcinoma","volume":"75","author":"Tian","year":"2015","journal-title":"Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.fct.2018.11.047","article-title":"Aflatoxin B1: A review on metabolism, toxicity, occurrence in food, occupational exposure, and detoxification methods","volume":"124","author":"Rushing","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1038\/sj.onc.1210279","article-title":"TP53 mutations and hepatocellular carcinoma: Insights into the etiology and pathogenesis of liver cancer","volume":"26","author":"Hussain","year":"2007","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Fang, Y., Feng, Y., Wu, T., Srinivas, S., Yang, W., Fan, J., Yang, C., and Wang, S. (2013). Aflatoxin B1 negatively regulates Wnt\/beta-catenin signaling pathway through activating miR-33a. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073004"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"16732","DOI":"10.1038\/srep16732","article-title":"miR-34a screened by miRNA profiling negatively regulates Wnt\/beta-catenin signaling pathway in Aflatoxin B1 induced hepatotoxicity","volume":"5","author":"Zhu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/mc.1041","article-title":"CTNNB1 mutations and beta-catenin protein accumulation in human hepatocellular carcinomas associated with high exposure to aflatoxin B1","volume":"31","author":"Devereux","year":"2001","journal-title":"Mol. Carcinog."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0002-9440(10)65168-1","article-title":"Nuclear accumulation of mutated beta-catenin in hepatocellular carcinoma is associated with increased cell proliferation","volume":"155","author":"Nhieu","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4997","DOI":"10.1158\/1078-0432.CCR-11-2322","article-title":"Wnt-pathway activation in two molecular classes of hepatocellular carcinoma and experimental modulation by sorafenib","volume":"18","author":"Lachenmayer","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/1097-0142(20010701)92:1<136::AID-CNCR1301>3.0.CO;2-R","article-title":"beta-Catenin mutation and overexpression in hepatocellular carcinoma: Clinicopathologic and prognostic significance","volume":"92","author":"Wong","year":"2001","journal-title":"Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"38999","DOI":"10.18632\/oncotarget.5738","article-title":"Identification of the beta-catenin\/JNK\/prothymosin-alpha axis as a novel target of sorafenib in hepatocellular carcinoma cells","volume":"6","author":"Lin","year":"2015","journal-title":"Oncotarget"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.1038\/sj.onc.1209547","article-title":"Genetics of hepatocellular tumors","volume":"25","year":"2006","journal-title":"Oncogene"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/ng.2291","article-title":"Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators","volume":"44","author":"Fujimoto","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_80","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_81","doi-asserted-by":"crossref","first-page":"S144","DOI":"10.1016\/j.jhep.2015.02.007","article-title":"Liver cancer: Approaching a personalized care","volume":"62","author":"Bruix","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/s41575-018-0075-9","article-title":"Wnt-beta-catenin signalling in liver development, health and disease","volume":"16","author":"Perugorria","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1038\/s41467-019-09780-z","article-title":"Promotion of growth factor signaling as a critical function of beta-catenin during HCC progression","volume":"10","author":"Kim","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/35094067","article-title":"APC, signal transduction and genetic instability in colorectal cancer","volume":"1","author":"Fodde","year":"2001","journal-title":"Nat. Rev. Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.jhep.2013.07.001","article-title":"Wnt signaling and hepatocarcinogenesis: Molecular targets for the development of innovative anticancer drugs","volume":"59","author":"Pez","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/hep.27558","article-title":"betaII-Spectrin (SPTBN1) suppresses progression of hepatocellular carcinoma and Wnt signaling by regulation of Wnt inhibitor kallistatin","volume":"61","author":"Zhi","year":"2015","journal-title":"Hepatology"},{"key":"ref_87","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_88","doi-asserted-by":"crossref","unstructured":"Jain, S., Chang, T.T., Hamilton, J.P., Lin, S.Y., Lin, Y.J., Evans, A.A., Selaru, F.M., Lin, P.W., Chen, S.H., and Block, T.M. (2011). Methylation of the CpG sites only on the sense strand of the APC gene is specific for hepatocellular carcinoma. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026799"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5357","DOI":"10.1007\/s13277-014-1698-2","article-title":"Activated macrophages promote Wnt\/beta-catenin signaling in cholangiocarcinoma cells","volume":"35","author":"Loilome","year":"2014","journal-title":"Tumour Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1172\/JCI76452","article-title":"WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited","volume":"125","author":"Boulter","year":"2015","journal-title":"J. Clin. Invest."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1002\/hep.26721","article-title":"Global alterations of DNA methylation in cholangiocarcinoma target the Wnt signaling pathway","volume":"59","author":"Goeppert","year":"2014","journal-title":"Hepatology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.biopha.2017.07.025","article-title":"Long noncoding RNA PCAT1 regulates extrahepatic cholangiocarcinoma progression via the Wnt\/beta-catenin-signaling pathway","volume":"94","author":"Zhang","year":"2017","journal-title":"Biomed Pharm."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1128\/MCB.00384-13","article-title":"Oncogenic activity of retinoic acid receptor gamma is exhibited through activation of the Akt\/NF-kappaB and Wnt\/beta-catenin pathways in cholangiocarcinoma","volume":"33","author":"Huang","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jhep.2017.02.017","article-title":"SOX17 regulates cholangiocyte differentiation and acts as a tumor suppressor in cholangiocarcinoma","volume":"67","author":"Lozano","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"18905","DOI":"10.18632\/oncotarget.4305","article-title":"Underexpression of LKB1 tumor suppressor is associated with enhanced Wnt signaling and malignant characteristics of human intrahepatic cholangiocarcinoma","volume":"6","author":"Wang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_96","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_97","doi-asserted-by":"crossref","first-page":"e26991","DOI":"10.1002\/pbc.26991","article-title":"A novel tissue-based ss-catenin gene and immunohistochemical analysis to exclude familial adenomatous polyposis among children with hepatoblastoma tumors","volume":"65","author":"Dubbink","year":"2018","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.cmet.2019.01.002","article-title":"Inhibiting Glutamine-Dependent mTORC1 Activation Ameliorates Liver Cancers Driven by beta-Catenin Mutations","volume":"29","author":"Ko","year":"2019","journal-title":"Cell Metab."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1476-4598-10-16","article-title":"Soluble Frizzled-7 receptor inhibits Wnt signaling and sensitizes hepatocellular carcinoma cells towards doxorubicin","volume":"10","author":"Wei","year":"2011","journal-title":"Mol. Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"7490","DOI":"10.1158\/1078-0432.CCR-17-2157","article-title":"A First-in-Human Phase I Study of the Anticancer Stem Cell Agent Ipafricept (OMP-54F28), a Decoy Receptor for Wnt Ligands, in Patients with Advanced Solid Tumors","volume":"23","author":"Jimeno","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_101","unstructured":"(2014, February 24). Dose Escalation Study of OMP-54F28 in Combination with Sorafenib in Patients With Hepatocellular Cancer, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02069145."},{"key":"ref_102","unstructured":"(2019, May 31). A Dose Escalation Study of OMP-54F28 in Subjects with Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01608867."},{"key":"ref_103","unstructured":"(2014, March 20). Dose Escalation Study of OMP-54F28 in Combination With Paclitaxel and Carboplatin in Patients With Recurrent Platinum-Sensitive Ovarian Cancer, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02092363."},{"key":"ref_104","unstructured":"(2014, January 30). Dose Escalation Study of OMP-54F28 in Combination With Nab-Paclitaxel and Gemcitabine in Patients with Previously Untreated Stage IV Pancreatic Cancer, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02050178."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Arafat, K., Iratni, R., Takahashi, T., Parekh, K., Al Dhaheri, Y., Adrian, T.E., and Attoub, S. (2013). Inhibitory Effects of Salinomycin on Cell Survival, Colony Growth, Migration, and Invasion of Human Non-Small Cell Lung Cancer A549 and LNM35: Involvement of NAG-1. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066931"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1002\/jcb.24850","article-title":"Salinomycin suppresses LRP6 expression and inhibits both Wnt\/beta-catenin and mTORC1 signaling in breast and prostate cancer cells","volume":"115","author":"Lu","year":"2014","journal-title":"J. Cell. Biochem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e1039","DOI":"10.1038\/cddis.2013.515","article-title":"Roles of Wnt\/beta-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment","volume":"5","author":"Mao","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.canlet.2011.07.016","article-title":"Salinomycin inhibits osteosarcoma by targeting its tumor stem cells","volume":"311","author":"Tang","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Wang, F., Dai, W., Wang, Y., Shen, M., Chen, K., Cheng, P., Zhang, Y., Wang, C., Li, J., and Zheng, Y. (2014). The synergistic in vitro and in vivo antitumor effect of combination therapy with salinomycin and 5-fluorouracil against hepatocellular carcinoma. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097414"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Wang, F., He, L., Dai, W.Q., Xu, Y.P., Wu, D., Lin, C.L., Wu, S.M., Cheng, P., Zhang, Y., and Shen, M. (2012). Salinomycin inhibits proliferation and induces apoptosis of human hepatocellular carcinoma cells in vitro and in vivo. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050638"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1476-4598-8-76","article-title":"Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells","volume":"8","author":"Wei","year":"2009","journal-title":"Mol. Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1038\/sj.onc.1208511","article-title":"Blockade of Wnt-1 signaling induces apoptosis in human colorectal cancer cells containing downstream mutations","volume":"24","author":"He","year":"2005","journal-title":"Oncogene"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S1476-5586(04)80048-4","article-title":"A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells","volume":"6","author":"He","year":"2004","journal-title":"Neoplasia"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Mikami, I., You, L., He, B., Xu, Z., Batra, S., Lee, A.Y., Mazieres, J., Reguart, N., Uematsu, K., and Koizumi, K. (2005). Efficacy of Wnt-1 monoclonal antibody in sarcoma cells. BMC Cancer, 5.","DOI":"10.1186\/1471-2407-5-53"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"6598","DOI":"10.1038\/sj.onc.1205920","article-title":"Wnt and frizzled receptors as potential targets for immunotherapy in head and neck squamous cell carcinomas","volume":"21","author":"Rhee","year":"2002","journal-title":"Oncogene"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"6951","DOI":"10.1158\/0008-5472.CAN-09-0541","article-title":"Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma","volume":"69","author":"Hu","year":"2009","journal-title":"Cancer Res."},{"key":"ref_117","unstructured":"(2011, October 24). A Study of DKN-01 in Multiple Myeloma or Advanced Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01457417."},{"key":"ref_118","unstructured":"(2012, October 22). A Study of DKN-01 and Lenalidomide\/Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01711671."},{"key":"ref_119","unstructured":"(2013, December 17). A Study of DKN-01 in Combination With Paclitaxel or Pembrolizumab (P102), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02013154."},{"key":"ref_120","unstructured":"(2015, March 03). Study of DKN-01 and Gemcitabine\/Cisplatin in Patients with Carcinoma to Primary to the Intra- or Extra-Hepatic Biliary System or Gallbladder, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02375880."},{"key":"ref_121","unstructured":"(2018, January 10). A Study of DKN-01 as a Monotherapy or in Combination With Paclitaxel in Patients with Recurrent Epithelial Endometrial or Epithelial Ovarian Cancer (P204), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03395080."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1200\/jco.2016.34.4_suppl.111","article-title":"A Phase 1 study of DKN-01, an anti-DKK1 antibody, in combination with paclitaxel (pac) in patients with DKK1 relapsed or refractory esophageal cancer (EC) or gastro-esophageal junction tumors (GEJ)","volume":"34","author":"Bendell","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_123","unstructured":"(2018, August 24). DKN-01 Inhibition in Advanced Liver Cancer, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03645980."},{"key":"ref_124","unstructured":"(2019, January 28). Combination of Targeted and Immunotherapy for Advanced Biliary Tract and Esophagogastric Gastric Cancer (DYNAMIC), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03818997."},{"key":"ref_125","unstructured":"(2016, February 05). CGX1321 in Subjects With Advanced Solid Tumors and CGX1321 with Pembrolizumab in Subjects With Advanced GI Tumors (Keynote 596), Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02675946."},{"key":"ref_126","unstructured":"(2018, April 25). Phase 1 Dose Escalation Study of CGX1321 in Subjects with Advanced Gastrointestinal Tumors, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03507998."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"14244","DOI":"10.1038\/s41598-018-32652-3","article-title":"Identification of RSPO2 Fusion Mutations and Target Therapy Using a Porcupine Inhibitor","volume":"8","author":"Li","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.neo.2016.10.004","article-title":"Blocking Wnt Secretion Reduces Growth of Hepatocellular Carcinoma Cell Lines Mostly Independent of beta-Catenin Signaling","volume":"18","author":"Wang","year":"2016","journal-title":"Neoplasia"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"25390","DOI":"10.18632\/oncotarget.4455","article-title":"Tankyrase inhibitors attenuate WNT\/beta-catenin signaling and inhibit growth of hepatocellular carcinoma cells","volume":"6","author":"Ma","year":"2015","journal-title":"Oncotarget"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Gwak, J., Lee, J.H., Chung, Y.H., Song, G.Y., and Oh, S. (2012). Small molecule-based promotion of PKCalpha-mediated beta-catenin degradation suppresses the proliferation of CRT-positive cancer cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046697"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1593\/neo.07469","article-title":"siRNA-mediated beta-catenin knockdown in human hepatoma cells results in decreased growth and survival","volume":"9","author":"Zeng","year":"2007","journal-title":"Neoplasia"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1073\/pnas.1424171112","article-title":"Suppression of cancer relapse and metastasis by inhibiting cancer stemness","volume":"112","author":"Li","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_133","unstructured":"(2011, February 24). Safety and Efficacy Study of PRI-724 in Subjects with Advanced Solid Tumors, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01302405."},{"key":"ref_134","unstructured":"(2012, May 25). Safety and Efficacy Study of PRI-724 in Subjects with Advanced Myeloid Malignancies, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01606579."},{"key":"ref_135","unstructured":"(2013, January 09). Safety and Efficacy Study of PRI-724 Plus Gemcitabine in Subjects with Advanced or Metastatic Pancreatic Adenocarcinoma, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01764477."},{"key":"ref_136","unstructured":"(2014, July 21). An Open Label, Single Arm, Dose Escalation Phase 1 Trial of PRI-724 in Patients with HCV-induced Cirrhosis, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02195440."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ebiom.2017.08.016","article-title":"Safety, Tolerability, and Preliminary Efficacy of the Anti-Fibrotic Small Molecule PRI-724, a CBP\/beta-Catenin Inhibitor, in Patients with Hepatitis C Virus-related Cirrhosis: A Single-Center, Open-Label, Dose Escalation Phase 1 Trial","volume":"23","author":"Kimura","year":"2017","journal-title":"EBioMed."},{"key":"ref_138","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_139","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"},{"key":"ref_140","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_141","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_142","doi-asserted-by":"crossref","unstructured":"Mologni, L., Brussolo, S., Ceccon, M., and Gambacorti-Passerini, C. (2012). Synergistic effects of combined Wnt\/KRAS inhibition in colorectal cancer cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051449"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.jhep.2010.07.020","article-title":"Pegylated interferon alpha targets Wnt signaling by inducing nuclear export of beta-catenin","volume":"54","author":"Thompson","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1053\/j.gastro.2018.11.001","article-title":"Genomic Medicine and Implications for Hepatocellular Carcinoma Prevention and Therapy","volume":"156","author":"Dhanasekaran","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jhep.2017.05.014","article-title":"Histological subtypes of hepatocellular carcinoma are related to gene mutations and molecular tumour classification","volume":"67","author":"Calderaro","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/hep.21467","article-title":"Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets","volume":"45","author":"Boyault","year":"2007","journal-title":"Hepatology"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/7\/926\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:01:46Z","timestamp":1760187706000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/11\/7\/926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,2]]},"references-count":146,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,7]]}},"alternative-id":["cancers11070926"],"URL":"https:\/\/doi.org\/10.3390\/cancers11070926","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,2]]}}}