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Dickkopf-1 promotes angiogenesis by upregulating VEGF receptor 2-mediated mTOR/p70S6K signaling in hepatocellular carcinoma

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dc.contributor.author김도영-
dc.contributor.author김범경-
dc.contributor.author김승업-
dc.contributor.author김혜미-
dc.contributor.author박준용-
dc.contributor.author박혜정-
dc.contributor.author안상훈-
dc.contributor.author이혜원-
dc.date.accessioned2022-02-23T01:01:19Z-
dc.date.available2022-02-23T01:01:19Z-
dc.date.issued2021-10-
dc.identifier.issn2156-6976-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/187497-
dc.description.abstractThe expression of Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling pathway, is upregulated in hepatocellular carcinoma (HCC). Here, we investigated the tumorigenic and angiogenic potential of DKK1 in HCC. Stable cell lines were established using the clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9)-based DKK1 knock-out system in Hep3B cells and the tetracycline-based DKK1 inducible system in Huh7 cells. Multicellular tumor spheroids (MCTSs) were cultured using Hep3B stable cells. We also employed xenografts generated using Hep3B stable cells and transgenic mouse models established using hydrodynamic tail vein injection. The angiogenic potential increased in HUVECs treated with CM from Huh7 stable cells with high DKK1 expression and Hep3B wild-type cells. DKK1 accelerated the downstream molecules of vascular endothelial growth factor receptor 2 (VEGFR2)-mediated mTOR/p70 S6 kinase (p70S6K) signaling. MCTSs generated using Hep3B wild-type cells promoted compact spheroid formation and increased the expression of CD31 and epithelial-mesenchymal transition (EMT) markers, and increased the VEGFR2-mediated mTOR/p70S6K signaling, compared to the controls (all P<0.01). Xenograft tumors generated using Hep3B cells with DKK1 knock-out (n=10) exhibited slower growth than, the controls (n=10) and the expression of Ki-67, VEGFR2, CD31 and EMT markers decreased (all P<0.05). In addition, forced DKK1 expression with HRAS in transgenic mouse livers (n=5) resulted in the formation of more tumors and increased expression of downstream molecules of VEGFR2-mediated mTOR/p70S6K signaling pathway as well as Ki67, CD31 and EMT markers (P<0.05), compared to that of the controls (n=5). Our findings indicate that DKK1 facilitates angiogenesis and tumorigenesis by upregulating VEGFR2-mediated mTOR/p70S6K signaling in HCC.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publishere-Century Publishing Corporation-
dc.relation.isPartOfAMERICAN JOURNAL OF CANCER RESEARCH-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleDickkopf-1 promotes angiogenesis by upregulating VEGF receptor 2-mediated mTOR/p70S6K signaling in hepatocellular carcinoma-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorSang Hyun Seo-
dc.contributor.googleauthorKyung Joo Cho-
dc.contributor.googleauthorHye Jung Park-
dc.contributor.googleauthorHyemi Kim-
dc.contributor.googleauthorHye Won Lee-
dc.contributor.googleauthorBeom Kyung Kim-
dc.contributor.googleauthorJun Yong Park-
dc.contributor.googleauthorDo Young Kim-
dc.contributor.googleauthorSang Hoon Ahn-
dc.contributor.googleauthorSeung Up Kim-
dc.contributor.localIdA00385-
dc.contributor.localIdA00487-
dc.contributor.localIdA00654-
dc.contributor.localIdA01170-
dc.contributor.localIdA01675-
dc.contributor.localIdA01769-
dc.contributor.localIdA02226-
dc.contributor.localIdA03318-
dc.relation.journalcodeJ00070-
dc.identifier.eissn2156-6976-
dc.identifier.pmid34765293-
dc.subject.keywordDickkopf-1-
dc.subject.keywordangiogenesis-
dc.subject.keywordepithelial-mesenchymal transition-
dc.subject.keywordhepatocellular carcinoma-
dc.subject.keywordvascular endothelial growth factor receptor 2-
dc.contributor.alternativeNameKim, Do Young-
dc.contributor.affiliatedAuthor김도영-
dc.contributor.affiliatedAuthor김범경-
dc.contributor.affiliatedAuthor김승업-
dc.contributor.affiliatedAuthor김혜미-
dc.contributor.affiliatedAuthor박준용-
dc.contributor.affiliatedAuthor박혜정-
dc.contributor.affiliatedAuthor안상훈-
dc.contributor.affiliatedAuthor이혜원-
dc.citation.volume11-
dc.citation.number10-
dc.citation.startPage4788-
dc.citation.endPage4806-
dc.identifier.bibliographicCitationAMERICAN JOURNAL OF CANCER RESEARCH, Vol.11(10) : 4788-4806, 2021-10-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

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