Please use this identifier to cite or link to this item:
|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|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jul 11, 2020
WEB OF SCIENCETM
checked on Jul 3, 2020
checked on Jul 11, 2020
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.