File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
  • Find via Find It@HKUL

Conference Paper: C-terminal truncated hepatitis B virus X protein promotes hepatocarcinogenesis through enhanced stemness and resistance to therapy

TitleC-terminal truncated hepatitis B virus X protein promotes hepatocarcinogenesis through enhanced stemness and resistance to therapy
Authors
KeywordsMedical sciences
Oncology
Issue Date2015
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
The 106th Annual Meeting of the American Association for Cancer Research (AACR 2015), Philadelphia, PA., 18-22 April 2015. In Cancer Research, 2015, v. 75 n. 15 suppl., abstract no. 2223 How to Cite?
AbstractTumor relapse after chemotherapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive initial treatment. Chronic infection with hepatitis B virus (HBV) has long been linked to the development of HCC. Upon chronic infection, random HBV genome integration can lead to truncation of hepatitis B virus X (HBx) protein at the C-terminus. The resulting C-terminal-truncated HBx (HBx-ΔC) was previously shown to confer enhanced invasiveness and diminished apoptotic response in HCC cells. In this study, we found HBx-ΔC to be more frequently detected in HCC clinical samples than their matched non-tumor counterparts. In addition, we also identified a strong positive correlation between HBx-ΔC and the liver cancer stem cell marker CD133, in a panel of liver cell line tested. Subsequently, we delineated the role of a naturally occurring HBx-ΔC (HBx-Δ14) in promoting stemness and aggressive behaviors in HCC cells. The stable overexpression of HBx-Δ14 in HCC cell line (Huh7) and immortalized normal liver cell line (MIHA) promoted expression of stemness markers, EpCAM and SOX2. In vitro functional studies with HBx-Δ14 stably overexpressed in Huh7 demonstrated an increased ability to self-renew, resist chemotherapy (5-fluorouracil) and targeted therapy (sorafenib), migrate and induce capillary tube formation in endothelial cells. Similar functional results were also obtained when HBx-Δ14 was stably overexpressed in MIHA cells. Taken together, in addition to its role in enhancing HCC metastasis, we find HBx-Δ14 to confer cancer and stem cell-like features in HCC, and to play an important role in driving tumor relapse in this deadly disease.
DescriptionThis journal suppl. entitled: Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA
Persistent Identifierhttp://hdl.handle.net/10722/214997
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorNg, KY-
dc.contributor.authorChai, S-
dc.contributor.authorTong, M-
dc.contributor.authorGuan, XY-
dc.contributor.authorCheng, AS-
dc.contributor.authorMa, S-
dc.date.accessioned2015-08-21T12:17:45Z-
dc.date.available2015-08-21T12:17:45Z-
dc.date.issued2015-
dc.identifier.citationThe 106th Annual Meeting of the American Association for Cancer Research (AACR 2015), Philadelphia, PA., 18-22 April 2015. In Cancer Research, 2015, v. 75 n. 15 suppl., abstract no. 2223-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/214997-
dc.descriptionThis journal suppl. entitled: Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA-
dc.description.abstractTumor relapse after chemotherapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive initial treatment. Chronic infection with hepatitis B virus (HBV) has long been linked to the development of HCC. Upon chronic infection, random HBV genome integration can lead to truncation of hepatitis B virus X (HBx) protein at the C-terminus. The resulting C-terminal-truncated HBx (HBx-ΔC) was previously shown to confer enhanced invasiveness and diminished apoptotic response in HCC cells. In this study, we found HBx-ΔC to be more frequently detected in HCC clinical samples than their matched non-tumor counterparts. In addition, we also identified a strong positive correlation between HBx-ΔC and the liver cancer stem cell marker CD133, in a panel of liver cell line tested. Subsequently, we delineated the role of a naturally occurring HBx-ΔC (HBx-Δ14) in promoting stemness and aggressive behaviors in HCC cells. The stable overexpression of HBx-Δ14 in HCC cell line (Huh7) and immortalized normal liver cell line (MIHA) promoted expression of stemness markers, EpCAM and SOX2. In vitro functional studies with HBx-Δ14 stably overexpressed in Huh7 demonstrated an increased ability to self-renew, resist chemotherapy (5-fluorouracil) and targeted therapy (sorafenib), migrate and induce capillary tube formation in endothelial cells. Similar functional results were also obtained when HBx-Δ14 was stably overexpressed in MIHA cells. Taken together, in addition to its role in enhancing HCC metastasis, we find HBx-Δ14 to confer cancer and stem cell-like features in HCC, and to play an important role in driving tumor relapse in this deadly disease.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.subjectMedical sciences-
dc.subjectOncology-
dc.titleC-terminal truncated hepatitis B virus X protein promotes hepatocarcinogenesis through enhanced stemness and resistance to therapy-
dc.typeConference_Paper-
dc.identifier.emailNg, KY: jkyng@hku.hk-
dc.identifier.emailTong, M: caroltm@hku.hk-
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hk-
dc.identifier.emailMa, S: stefma@hku.hk-
dc.identifier.authorityGuan, XY=rp00454-
dc.identifier.authorityMa, S=rp00506-
dc.identifier.hkuros248966-
dc.identifier.volume75-
dc.identifier.issue15 suppl.-
dc.publisher.placeUnited States-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats