完整後設資料紀錄
DC 欄位語言
dc.contributor.authorSu, Zhong-Liangen_US
dc.contributor.authorSu, Chien-Weien_US
dc.contributor.authorHuang, Yi-Luenen_US
dc.contributor.authorYang, Wan-Yuen_US
dc.contributor.authorSampurna, Bonifasius Puteraen_US
dc.contributor.authorOuchi, Toruen_US
dc.contributor.authorLee, Kuan-Linen_US
dc.contributor.authorWu, Chen-Shengen_US
dc.contributor.authorWang, Horng-Daren_US
dc.contributor.authorYuh, Chiou-Hwaen_US
dc.date.accessioned2019-12-13T01:09:58Z-
dc.date.available2019-12-13T01:09:58Z-
dc.date.issued2019-06-26en_US
dc.identifier.urihttp://dx.doi.org/10.3390/cancers11070927en_US
dc.identifier.urihttp://hdl.handle.net/11536/153053-
dc.description.abstractAurora A kinase (AURKA) is an important regulator in mitotic progression and is overexpressed frequently in human cancers, including hepatocellular carcinoma (HCC). Many AURKA mutations were identified in cancer patients. Overexpressing wild-type Aurka developed a low incidence of hepatic tumors after long latency in mice. However, none of the AURKA mutant animal models have ever been described. The mechanism of mutant AURKA-mediated hepatocarcinogenesis is still unclear. A novel AURKA mutation with a.a.352 Valine to Isoleucine (V352I) was identified from clinical specimens. By using liver-specific transgenic fish overexpressing both the mutant and wild-type AURKA, the AURKA(V352I)-induced hepatocarcinogenesis was earlier and much more severe than wild-type AURKA. Although an increase of the expression of lipogenic enzyme and lipogenic factor was observed in both AURKA(V352I) and AURKA(WT) transgenic fish, AURKA(V352I) has a greater probability to promote fibrosis at 3 months compared to AURKA(WT). Furthermore, the expression levels of cell cycle/proliferation markers were higher in the AURKA(V352I) mutant than AURKA(WT) in transgenic fish, implying that the AURKA(V352I) mutant may accelerate HCC progression. Moreover, we found that the AURKA(V352I) mutant activates AKT signaling and increases nuclear beta-catenin, but AURKA(WT) only activates membrane form beta-catenin, which may account for the differences. In this study, we provide a new insight, that the AURKA(V352I) mutation contributes to early onset hepatocarcinogenesis, possibly through activation of different pathways than AURKA(WT). This transgenic fish may serve as a drug-screening platform for potential precision medicine therapeutics.en_US
dc.language.isoen_USen_US
dc.subjecthepatocellular carcinoma (HCC)en_US
dc.subjectzebrafishen_US
dc.subjectAurora A kinase (AURKA)en_US
dc.subjectbeta-cateninen_US
dc.subjectAKT signaling pathwayen_US
dc.titleA Novel AURKA Mutant-Induced Early-Onset Severe Hepatocarcinogenesis Greater than Wild-Type via Activating Different Pathways in Zebrafishen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cancers11070927en_US
dc.identifier.journalCANCERSen_US
dc.citation.volume11en_US
dc.citation.issue7en_US
dc.citation.spage0en_US
dc.citation.epage0en_US
dc.contributor.department生物科技學系zh_TW
dc.contributor.departmentDepartment of Biological Science and Technologyen_US
dc.identifier.wosnumberWOS:000479322800038en_US
dc.citation.woscount0en_US
顯示於類別:期刊論文