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- Publisher Website: 10.1038/s41388-019-0704-y
- Scopus: eid_2-s2.0-85060926266
- PMID: 30696957
- WOS: WOS:000468740200007
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Article: Lymphoid enhancer-binding factor-1 promotes stemness and poor differentiation of hepatocellular carcinoma by directly activating the NOTCH pathway
Title | Lymphoid enhancer-binding factor-1 promotes stemness and poor differentiation of hepatocellular carcinoma by directly activating the NOTCH pathway |
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Authors | |
Issue Date | 2019 |
Publisher | Springer Nature [academic journals on nature.com]. 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? |
Abstract | The 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 Identifier | http://hdl.handle.net/10722/274905 |
ISSN | 2023 Impact Factor: 6.9 2023 SCImago Journal Rankings: 2.334 |
ISI Accession Number ID | |
Grants |
DC Field | Value | Language |
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dc.contributor.author | Fang, S | - |
dc.contributor.author | Liu, M | - |
dc.contributor.author | Li, L | - |
dc.contributor.author | Zhang, F | - |
dc.contributor.author | Yan, Q | - |
dc.contributor.author | Li, Y | - |
dc.contributor.author | Cui, Y | - |
dc.contributor.author | Zhu, YH | - |
dc.contributor.author | Yuan, YF | - |
dc.contributor.author | Guan, X | - |
dc.date.accessioned | 2019-09-10T02:31:18Z | - |
dc.date.available | 2019-09-10T02:31:18Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Oncogene, 2019, v. 38 n. 21, p. 4061-4074 | - |
dc.identifier.issn | 0950-9232 | - |
dc.identifier.uri | http://hdl.handle.net/10722/274905 | - |
dc.description.abstract | The 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.language | eng | - |
dc.publisher | Springer Nature [academic journals on nature.com]. The Journal's web site is located at http://www.nature.com/onc | - |
dc.relation.ispartof | Oncogene | - |
dc.title | Lymphoid enhancer-binding factor-1 promotes stemness and poor differentiation of hepatocellular carcinoma by directly activating the NOTCH pathway | - |
dc.type | Article | - |
dc.identifier.email | Guan, X: xyguan@hku.hk | - |
dc.identifier.authority | Guan, X=rp00454 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1038/s41388-019-0704-y | - |
dc.identifier.pmid | 30696957 | - |
dc.identifier.scopus | eid_2-s2.0-85060926266 | - |
dc.identifier.hkuros | 302607 | - |
dc.identifier.volume | 38 | - |
dc.identifier.issue | 21 | - |
dc.identifier.spage | 4061 | - |
dc.identifier.epage | 4074 | - |
dc.identifier.isi | WOS:000468740200007 | - |
dc.publisher.place | United Kingdom | - |
dc.relation.project | A Multidisciplinary Study on CD133 Liver Cancer Stem Cells: Molecular Mechanisms, Clinical Relevance and Therapeutic Implications | - |
dc.identifier.issnl | 0950-9232 | - |