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Conference Paper: Dishevelled 3 (Dvl3) is upregulated and enhances cell migration and invasion in hepatocellular carcinoma

TitleDishevelled 3 (Dvl3) is upregulated and enhances cell migration and invasion in hepatocellular carcinoma
Authors
Issue Date2011
PublisherAmerican Association for Cancer Research.
Citation
The 102nd Annual Meeting of the American Association for Cancer Reseach (AACR 2011), Orlando, FL., 2-6 April 2011. How to Cite?
AbstractHepatocellular carcinoma (HCC) is one of the most common fatal malignancies in the world and is particularly prevalent in China and Southeast Asia. Although the risk factors are well known, the molecular mechanisms underlying hepatocarcinogenesis is unclear. Alteration of Wnt signaling pathway is one of the key events in HCC development and so we performed a low-density array (LDA) analysis on 38 pairs of HCC samples and their corresponding non-tumorous livers to examine the expression profiles of different Wnt signaling components. We found that, among the genes studied, Dishevelled 3 (Dvl3) was significantly overexpressed in HCCs as compared with the corresponding non-tumorous liver tissues. In addition, Dvl3 overexpression in HCC was significantly associated with presence of venous invasion (P = .021). The overexpression result was confirmed by expansion of the sample size using quantitative real-time PCR (q-PCR). Next, we investigated the effects of Dvl3 on the migratory and invasive abilities of HCC cells. We established stable shRNA Dvl3-knockdown clones in PLC/PRF/5 HCC cells and found that knockdown of Dvl3 suppressed the migratory and invasive abilities of HCC cells using transwell migration and invasion assays, respectively, suggesting an enhancing role of Dvl3 in HCC cell movement and cell invasion. Although cell proliferation assay in vitro showed no significant difference between the stable Dvl3 knockdown and non-target control PLC/PRF/5 cells, in vivo study in SCID mice showed that the stable Dvl3-knockdown cells resulted in a lower incidence of tumors formed and a smaller tumor size. Furthermore, since Dvl3 is an upstream regulator of the Wnt/β-catenin pathway, using the TOPFOP luciferase reporter assay, we found that transient transfection of Dvl3 in PLC/PRF/5 and BEL-7402 HCC cell lines enhanced the β-catenin-dependent transcriptional activity. In conclusion, upregulation of Dvl3 was frequent in human HCCs. Dvl3 enhanced cell migration and invasion in vitro and tumorigenicity in vivo in SCID mice, and activated canonical β-catenin pathway. It may play an oncogenic role in HCC development.
DescriptionPoster Session 4 - Cytoplasmic Signal Transducers: abstract no. 1074
Persistent Identifierhttp://hdl.handle.net/10722/136002

 

DC FieldValueLanguage
dc.contributor.authorTsui, YMen_US
dc.contributor.authorTung, EKKen_US
dc.contributor.authorMak, CKMen_US
dc.contributor.authorNg, IOLen_US
dc.date.accessioned2011-07-27T02:01:19Z-
dc.date.available2011-07-27T02:01:19Z-
dc.date.issued2011en_US
dc.identifier.citationThe 102nd Annual Meeting of the American Association for Cancer Reseach (AACR 2011), Orlando, FL., 2-6 April 2011.en_US
dc.identifier.urihttp://hdl.handle.net/10722/136002-
dc.descriptionPoster Session 4 - Cytoplasmic Signal Transducers: abstract no. 1074-
dc.description.abstractHepatocellular carcinoma (HCC) is one of the most common fatal malignancies in the world and is particularly prevalent in China and Southeast Asia. Although the risk factors are well known, the molecular mechanisms underlying hepatocarcinogenesis is unclear. Alteration of Wnt signaling pathway is one of the key events in HCC development and so we performed a low-density array (LDA) analysis on 38 pairs of HCC samples and their corresponding non-tumorous livers to examine the expression profiles of different Wnt signaling components. We found that, among the genes studied, Dishevelled 3 (Dvl3) was significantly overexpressed in HCCs as compared with the corresponding non-tumorous liver tissues. In addition, Dvl3 overexpression in HCC was significantly associated with presence of venous invasion (P = .021). The overexpression result was confirmed by expansion of the sample size using quantitative real-time PCR (q-PCR). Next, we investigated the effects of Dvl3 on the migratory and invasive abilities of HCC cells. We established stable shRNA Dvl3-knockdown clones in PLC/PRF/5 HCC cells and found that knockdown of Dvl3 suppressed the migratory and invasive abilities of HCC cells using transwell migration and invasion assays, respectively, suggesting an enhancing role of Dvl3 in HCC cell movement and cell invasion. Although cell proliferation assay in vitro showed no significant difference between the stable Dvl3 knockdown and non-target control PLC/PRF/5 cells, in vivo study in SCID mice showed that the stable Dvl3-knockdown cells resulted in a lower incidence of tumors formed and a smaller tumor size. Furthermore, since Dvl3 is an upstream regulator of the Wnt/β-catenin pathway, using the TOPFOP luciferase reporter assay, we found that transient transfection of Dvl3 in PLC/PRF/5 and BEL-7402 HCC cell lines enhanced the β-catenin-dependent transcriptional activity. In conclusion, upregulation of Dvl3 was frequent in human HCCs. Dvl3 enhanced cell migration and invasion in vitro and tumorigenicity in vivo in SCID mice, and activated canonical β-catenin pathway. It may play an oncogenic role in HCC development.-
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofAnnual Meeting of the American Association for Cancer Reseachen_US
dc.titleDishevelled 3 (Dvl3) is upregulated and enhances cell migration and invasion in hepatocellular carcinomaen_US
dc.typeConference_Paperen_US
dc.identifier.emailTsui, YM: h0994002@HKUSUC.hku.hken_US
dc.identifier.emailTung, EKK: edmund@pathology.hku.hken_US
dc.identifier.emailMak, CKM: carmak@hku.hken_US
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros187383en_US
dc.description.otherThe 102nd Annual Meeting of the American Association for Cancer Reseach (AACR 2011), Orlando, FL., 2-6 April 2011.-

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