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Article: Lymphoid enhancer-binding factor-1 promotes stemness and poor differentiation of hepatocellular carcinoma by directly activating the NOTCH pathway

TitleLymphoid enhancer-binding factor-1 promotes stemness and poor differentiation of hepatocellular carcinoma by directly activating the NOTCH pathway
Authors
Issue Date2019
PublisherSpringer Nature [academic journals on nature.com]: Hybrid Journal. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2019, v. 38 n. 21, p. 4061-4074 How to Cite?
AbstractThe poorly differentiated hepatocellular carcinoma (HCC) cells are usually characterized by immature hepatic progenitor cell-like properties, such as enhanced self-renewal ability, resistance to chemotherapeutic drugs, and a loss of mature hepatocyte proteins. However, the molecular mechanisms governing this process still remain unclear. In this study, we found the lymphoid enhancer-binding factor-1 (LEF1), a transcriptional factor, was frequently overexpressed in HCCs, which was significantly associated with poor prognosis and tumor cell differentiation. Functional studies have found that LEF1 enhanced cell growth, foci formation, colony formation in soft agar, and tumor formation in nude mice. Different from its canonical roles in the WNT signaling pathway, we found that LEF1 could activate the critical members (e.g., NOTCH1 and NOTCH2) of the NOTCH signaling pathway through directly binding to their promoter regions. Further studies have found that LEF1 could enhance the self-renewal ability, drug resistance, dedifferentiation, and invasion of HCC cells. The oncogenic functions and the effects of LEF1 on cancer stemness could be effectively inhibited by NOTCH inhibitor. Further characterization of LEF1 may lead to the development of novel therapeutic strategies for HCC treatment. © 2019, Springer Nature Limited.
Persistent Identifierhttp://hdl.handle.net/10722/274905
ISSN
2017 Impact Factor: 6.854
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFang, S-
dc.contributor.authorLiu, M-
dc.contributor.authorLi, L-
dc.contributor.authorZhang, F-
dc.contributor.authorYan, Q-
dc.contributor.authorLi, Y-
dc.contributor.authorCui, Y-
dc.contributor.authorZhu, YH-
dc.contributor.authorYuan, YF-
dc.contributor.authorGuan, X-
dc.date.accessioned2019-09-10T02:31:18Z-
dc.date.available2019-09-10T02:31:18Z-
dc.date.issued2019-
dc.identifier.citationOncogene, 2019, v. 38 n. 21, p. 4061-4074-
dc.identifier.issn0950-9232-
dc.identifier.urihttp://hdl.handle.net/10722/274905-
dc.description.abstractThe poorly differentiated hepatocellular carcinoma (HCC) cells are usually characterized by immature hepatic progenitor cell-like properties, such as enhanced self-renewal ability, resistance to chemotherapeutic drugs, and a loss of mature hepatocyte proteins. However, the molecular mechanisms governing this process still remain unclear. In this study, we found the lymphoid enhancer-binding factor-1 (LEF1), a transcriptional factor, was frequently overexpressed in HCCs, which was significantly associated with poor prognosis and tumor cell differentiation. Functional studies have found that LEF1 enhanced cell growth, foci formation, colony formation in soft agar, and tumor formation in nude mice. Different from its canonical roles in the WNT signaling pathway, we found that LEF1 could activate the critical members (e.g., NOTCH1 and NOTCH2) of the NOTCH signaling pathway through directly binding to their promoter regions. Further studies have found that LEF1 could enhance the self-renewal ability, drug resistance, dedifferentiation, and invasion of HCC cells. The oncogenic functions and the effects of LEF1 on cancer stemness could be effectively inhibited by NOTCH inhibitor. Further characterization of LEF1 may lead to the development of novel therapeutic strategies for HCC treatment. © 2019, Springer Nature Limited.-
dc.languageeng-
dc.publisherSpringer Nature [academic journals on nature.com]: Hybrid Journal. The Journal's web site is located at http://www.nature.com/onc-
dc.relation.ispartofOncogene-
dc.titleLymphoid enhancer-binding factor-1 promotes stemness and poor differentiation of hepatocellular carcinoma by directly activating the NOTCH pathway-
dc.typeArticle-
dc.identifier.emailGuan, X: xyguan@hku.hk-
dc.identifier.authorityGuan, X=rp00454-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/s41388-019-0704-y-
dc.identifier.pmid30696957-
dc.identifier.scopuseid_2-s2.0-85060926266-
dc.identifier.hkuros302607-
dc.identifier.volume38-
dc.identifier.issue21-
dc.identifier.spage4061-
dc.identifier.epage4074-
dc.identifier.isiWOS:000468740200007-
dc.publisher.placeUnited Kingdom-

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