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|Title:||Oncofetal gene SALL4 in aggressive hepatocellular carcinoma||Authors:||Yong, K.J.
|Issue Date:||2013||Citation:||Yong, K.J., Gao, C., Lim, J.S.J., Yan, B., Yang, H., Dimitrov, T., Kawasaki, A., Ong, C.W., Wong, K.-F., Lee, S., Ravikumar, S., Srivastava, S., Tian, X., Poon, R.T., Fan, S.T., Luk, J.M., Dan, Y.Y., Salto-Tellez, M., Chai, L., Tenen, D.G. (2013). Oncofetal gene SALL4 in aggressive hepatocellular carcinoma. New England Journal of Medicine 368 (24) : 2266-2276. ScholarBank@NUS Repository. https://doi.org/10.1056/NEJMoa1300297||Abstract:||BACKGROUND: 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. Copyright © 2013 Massachusetts Medical Society.||Source Title:||New England Journal of Medicine||URI:||http://scholarbank.nus.edu.sg/handle/10635/110764||ISSN:||00284793||DOI:||10.1056/NEJMoa1300297|
|Appears in Collections:||Staff Publications|
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