https://scholars.lib.ntu.edu.tw/handle/123456789/581889
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Hu M.-H. | en_US |
dc.contributor.author | Chen L.-J. | en_US |
dc.contributor.author | Chen Y.-L. | en_US |
dc.contributor.author | Tsai M.-S. | en_US |
dc.contributor.author | Shiau C.-W. | en_US |
dc.contributor.author | Chao T.-I. | en_US |
dc.contributor.author | Liu C.-Y. | en_US |
dc.contributor.author | JIA-HORNG KAO | en_US |
dc.contributor.author | Chen K.-F. | en_US |
dc.date.accessioned | 2021-09-04T06:11:06Z | - |
dc.date.available | 2021-09-04T06:11:06Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85020407244&doi=10.18632%2foncotarget.17779&partnerID=40&md5=a4355444b818b0559c59e4241a13061f | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/581889 | - |
dc.description.abstract | Sorafenib is a multiple kinase inhibitor which targets Raf kinases, VEGFR, and PDGFR and is approved for the treatment of hepatocellular carcinoma (HCC). Previously, we found that p-STAT3 is a major target of SC-43, a sorafenib derivative. In this study, we report that SC-43-induced apoptosis in cholangiocarcinoma (CCA) via a novel mechanism. Three CCA cell lines (HuCCT-1, KKU-100 and CGCCA) were treated with SC-43 to determine their sensitivity to SC-43-induced cell death and apoptosis. We found that SC-43 activated SH2 domain-containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream cyclin B1 and Cdc2 downregulation, which induced G2-M arrest and apoptotic cell death. Importantly, SC-43 augmented SHP-1 activity by direct binding to N-SH2 and relief of its autoinhibition. Deletion of the N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 counteracted the effect of SC-43-induced SHP-1 phosphatase activation and antiproliferation ability in CCA cells. In vivo assay revealed that SC-43 exhibited xenograft tumor growth inhibition, p-STAT3 reduction and SHP-1 activity elevation. In conclusion, SC-43 induced apoptosis in CCA cells through the SHP-1/STAT3 signaling pathway. ? Hu et al. | - |
dc.publisher | Impact Journals LLC | - |
dc.relation.ispartof | Oncotarget | - |
dc.subject | Cholangiocarcinoma; Inflammatory cancer; SC-43; SHP-1; STAT3 | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | cyclin B1; cyclin dependent kinase 1; protein tyrosine phosphatase SHP 1; sc 43; sorafenib; STAT3 protein; unclassified drug; animal experiment; animal model; animal tissue; antiproliferative activity; apoptosis; Article; bile duct carcinoma; cancer inhibition; cell proliferation; cell viability; CGCCA 100 cell line; cholangiocarcinoma cell line; controlled study; down regulation; drug binding; drug mechanism; drug sensitivity; enzyme activation; G2 phase cell cycle checkpoint; HuCCT 1 cell line; human; human cell; human tissue; immunohistochemistry; in vivo study; KKU 100 cell line; male; mouse; nonhuman; point mutation; protein domain; signal transduction; tumor xenograft; Western blotting | - |
dc.title | Targeting SHP-1-STAT3 signaling: A promising therapeutic approach for the treatment of cholangiocarcinoma | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.18632/oncotarget.17779 | - |
dc.identifier.scopus | 2-s2.0-85020407244 | - |
dc.relation.pages | 65077-65089 | - |
dc.relation.journalvolume | 8 | - |
dc.relation.journalissue | 39 | - |
item.fulltext | no fulltext | - |
item.cerifentitytype | Publications | - |
item.openairetype | journal article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.grantfulltext | none | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.dept | Internal Medicine-NTUH | - |
crisitem.author.orcid | 0000-0002-2442-7952 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
顯示於: | 臨床醫學研究所 |
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