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Article: Oncofetal gene SALL4 in aggressive hepatocellular carcinoma

TitleOncofetal gene SALL4 in aggressive hepatocellular carcinoma
Authors
Issue Date2013
PublisherMassachusetts Medical Society. The Journal's web site is located at http://content.nejm.org/
Citation
New England Journal of Medicine, 2013, v. 368 n. 24, p. 2266-2276 How to Cite?
AbstractBACKGROUND: Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment. METHODS: We screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays. RESULTS: SALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult liver, but it is reexpressed in a subgroup of patients who have hepatocellular carcinoma and an unfavorable prognosis. Gene-expression analysis showed the enrichment of progenitor-like gene signatures with overexpression of proliferative and metastatic genes in SALL4-positive hepatocellular carcinomas. Loss-of-function studies confirmed the critical role of SALL4 in cell survival and tumorigenicity. Blocking SALL4–corepressor interactions released suppression of PTEN (the phosphatase and tensin homologue protein) and inhibited tumor formation in xenograft models in vivo. CONCLUSIONS: SALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype. The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma. (Funded by the Singapore National Medical Research Council and others.)
Persistent Identifierhttp://hdl.handle.net/10722/186350
ISSN
2019 Impact Factor: 74.699
2015 SCImago Journal Rankings: 14.619
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYong, KJ-
dc.contributor.authorGao, C-
dc.contributor.authorLim, JS-
dc.contributor.authorYan, B-
dc.contributor.authorYang, H-
dc.contributor.authorDimitrov, T-
dc.contributor.authorKawasaki, A-
dc.contributor.authorOng, CW-
dc.contributor.authorWong, K-
dc.contributor.authorLee, S-
dc.contributor.authorRavikumar, S-
dc.contributor.authorSrivastava, S-
dc.contributor.authorTian, X-
dc.contributor.authorPoon, RTP-
dc.contributor.authorFan, ST-
dc.contributor.authorLuk, JMC-
dc.contributor.authorDan, YY-
dc.contributor.authorSalto-Tellez, M-
dc.contributor.authorChai, L-
dc.contributor.authorTenen, DG-
dc.date.accessioned2013-08-20T12:03:49Z-
dc.date.available2013-08-20T12:03:49Z-
dc.date.issued2013-
dc.identifier.citationNew England Journal of Medicine, 2013, v. 368 n. 24, p. 2266-2276-
dc.identifier.issn0028-4793-
dc.identifier.urihttp://hdl.handle.net/10722/186350-
dc.description.abstractBACKGROUND: Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment. METHODS: We screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays. RESULTS: SALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult liver, but it is reexpressed in a subgroup of patients who have hepatocellular carcinoma and an unfavorable prognosis. Gene-expression analysis showed the enrichment of progenitor-like gene signatures with overexpression of proliferative and metastatic genes in SALL4-positive hepatocellular carcinomas. Loss-of-function studies confirmed the critical role of SALL4 in cell survival and tumorigenicity. Blocking SALL4–corepressor interactions released suppression of PTEN (the phosphatase and tensin homologue protein) and inhibited tumor formation in xenograft models in vivo. CONCLUSIONS: SALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype. The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma. (Funded by the Singapore National Medical Research Council and others.)-
dc.languageeng-
dc.publisherMassachusetts Medical Society. The Journal's web site is located at http://content.nejm.org/-
dc.relation.ispartofNew England Journal of Medicine-
dc.rightsFrom New England Journal of Medicine, Kol Jia Yong, Chong Gao, Joline S.J. Lim, et al., Oncofetal Gene SALL4 in Aggressive Hepatocellular Carcinoma, vol. 368, p. 2266-2276. Copyright © 2013 Massachusetts Medical Society. Reprinted with permission.-
dc.titleOncofetal gene SALL4 in aggressive hepatocellular carcinoma-
dc.typeArticle-
dc.identifier.emailPoon, RTP: poontp@hku.hk-
dc.identifier.emailFan, ST: stfan@hku.hk-
dc.identifier.emailLuk, JMC: jmluk@hku.hk-
dc.identifier.authorityPoon, RTP=rp00446-
dc.identifier.authorityFan, ST=rp00355-
dc.identifier.authorityLuk, JMC=rp00349-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1056/NEJMoa1300297-
dc.identifier.pmid23758232-
dc.identifier.pmcidPMC3781214-
dc.identifier.scopuseid_2-s2.0-84878887042-
dc.identifier.hkuros220040-
dc.identifier.volume368-
dc.identifier.issue24-
dc.identifier.spage2266-
dc.identifier.epage2276-
dc.identifier.isiWOS:000320230500002-
dc.publisher.placeUnited States-
dc.identifier.f1000718019311-

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