Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/90294
DC Field | Value | Language |
---|---|---|
dc.contributor | Department of Applied Biology and Chemical Technology | en_US |
dc.creator | Leung, HW | en_US |
dc.creator | Leung, CON | en_US |
dc.creator | Lau, EY | en_US |
dc.creator | Chung, KPS | en_US |
dc.creator | Mok, EH | en_US |
dc.creator | Lei, MML | en_US |
dc.creator | Leung, RWH | en_US |
dc.creator | Tong, M | en_US |
dc.creator | Keng, VW | en_US |
dc.creator | Ma, C | en_US |
dc.creator | Zhao, Q | en_US |
dc.creator | Ng, IOL | en_US |
dc.creator | Ma, S | en_US |
dc.creator | Lee, TK | en_US |
dc.date.accessioned | 2021-06-10T06:54:53Z | - |
dc.date.available | 2021-06-10T06:54:53Z | - |
dc.identifier.issn | 0008-5472 | en_US |
dc.identifier.uri | http://hdl.handle.net/10397/90294 | - |
dc.language.iso | en | en_US |
dc.publisher | American Association for Cancer Research | en_US |
dc.rights | ©2021 American Association for Cancer Research. | en_US |
dc.rights | The following publication Leung, H. W., Leung, C. O. N., Lau, E. Y., Chung, K. P. S., Mok, E. H., Lei, M. M. L., . . . Lee, T. K. (2021). EPHB2 activates β-catenin to enhance cancer stem cell properties and drive sorafenib resistance in hepatocellular carcinoma. Cancer Research, 81(12), 3229-3240 is available at https://dx.doi.org/10.1158/0008-5472.CAN-21-0184. | en_US |
dc.title | EPHB2 activates β-catenin to enhance cancer stem cell properties and drive sorafenib resistance in hepatocellular carcinoma | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.spage | 3329 | en_US |
dc.identifier.epage | 3340 | en_US |
dc.identifier.volume | 81 | en_US |
dc.identifier.issue | 12 | en_US |
dc.identifier.doi | 10.1158/0008-5472.CAN-21-0184 | en_US |
dcterms.abstract | The survival benefit derived from sorafenib treatment for patients with hepatocellular carcinoma (HCC) is modest due to acquired resistance. Targeting cancer stem cells (CSC) is a possible way to reverse drug resistance; however, inhibitors that specifically target liver CSCs are limited. In this study, we established two sorafenib-resistant, patient-derived tumor xenografts (PDX) that mimicked development of acquired resistance to sorafenib in HCC patients. RNA-sequencing analysis of sorafenib-resistant PDXs and their corresponding mock controls identified EPHB2 as the most significantly upregulated kinase. EPHB2 expression increased stepwise from normal liver tissue to fibrotic liver tissue to HCC tissue and correlated with poor prognosis. Endogenous EPHB2 knockout showed attenuation of tumor development in mice. EPHB2 regulated the traits of liver CSCs; similarly, sorted EPHB2High HCC cells were endowed with enhanced CSC properties when compared with their EPHB2Low counterparts. Mechanistically, EPHB2 regulated cancer stemness and drug resistance by driving the SRC/AKT/GSK3β/β-catenin signaling cascade, and EPHB2 expression was regulated by TCF1 via promoter activation, forming a positive Wnt/β-catenin feedback loop. Intravenous administration of rAAV-8-shEPHB2 suppressed HCC tumor growth and significantly sensitized HCC cells to sorafenib in an NRAS/AKT-driven HCC immunocompetent mouse model. Targeting a positive feedback loop involving the EPHB2/β-catenin axis may be a possible therapeutic strategy to combat acquired drug resistance in HCC. | en_US |
dcterms.accessRights | open access | en_US |
dcterms.bibliographicCitation | Cancer research, 15 June 2021, v. 81, no. 12, p. 3229-3240. | en_US |
dcterms.isPartOf | Cancer research | en_US |
dcterms.issued | 2021-06-15 | - |
dc.identifier.scopus | 2-s2.0-85108104521 | - |
dc.identifier.eissn | 1538-7445 | en_US |
dc.description.validate | 202106 bcvc | en_US |
dc.description.oa | Accepted Manuscript | en_US |
dc.identifier.FolderNumber | a0913-n01, a1174-n01, ABCT-0100 | - |
dc.identifier.SubFormID | 2128, 44074 | - |
dc.description.fundingSource | RGC | en_US |
dc.description.fundingSource | Others | en_US |
dc.description.fundingText | Theme-based Research Scheme project; Project of Strategic Importance, PolyU; Research Impact Fund | en_US |
dc.description.pubStatus | Published | en_US |
dc.identifier.OPUS | 50674690 | - |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Leung_et_al._EPHB2_Cancer_Research.pdf | Pre-Published version | 488.14 kB | Adobe PDF | View/Open |
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