Skip navigation
  • 中文
  • English

DSpace CRIS

  • DSpace logo
  • Home
  • Organizations
  • Researchers
  • Research Outputs
  • Explore by
    • Organizations
    • Researchers
    • Research Outputs
  • Academic & Publications
  • Sign in
  • 中文
  • English
  1. NTU Scholars
  2. 醫學院
  3. 臨床醫學研究所
Please use this identifier to cite or link to this item: https://scholars.lib.ntu.edu.tw/handle/123456789/581824
Title: Serine/threonine protein phosphatase 5 is a potential therapeutic target in cholangiocarcinoma
Authors: Hu M.-H.
Huang T.-T.
Chao T.-I.
Chen L.-J.
Chen Y.-L.
Tsai M.-H.
Liu C.-Y.
JIA-HORNG KAO 
Chen K.-F.
Keywords: AMP-activated protein kinase; cantharidin; cholangiocarcinoma; protein phosphatase 5
Issue Date: 2018
Publisher: Blackwell Publishing Ltd
Journal Volume: 38
Journal Issue: 12
Start page/Pages: 2248-2259
Source: Liver International
Abstract: 
Background & Aims: Few molecules are currently verified to be actionable drug targets in cholangiocarcinoma (CCA). Serine/threonine protein phosphatase 5 (PP5) dysregulation is related to several malignancies. However, the role of PP5 in CCA is poorly defined. Methods: Colony and tumorsphere formation assays were conducted to establish the role of PP5 in CCA tumorigenesis. Cantharidin (CTD) and norcantharidin (NCTD), both potent PP5 inhibitors, were used in in vitro and in vivo experiments to validate the potential therapeutic role of PP5. Results: Increased cell growth, colony formation and tumorsphere formation were observed in PP5-overexpressing CCA cells, whereas PP5 knockdown by shRNA decreased cell growth and colony formation. Tumours from HuCCT1 xenograft-bearing mice treated with PP5-shRNA showed decreased growth and increased AMP-activated protein kinase (AMPK) phosphorylation. Furthermore, CTD treatment decreased cell viability, reduced PP5 activity and enhanced AMPK phosphorylation in CCA cell lines. Overexpressing PP5 or enhancing PP5 activity suppressed AMPK phosphorylation and decreased CTD-induced cell death. Suppressing p-AMPK with siRNA or inhibitors also decreased CTD-induced cell death, suggesting a pivotal role for PP5-AMPK cascades in CCA. Immunoprecipitation revealed that PP5 interacted with AMPK. Importantly, treatment of HuCCT1 xenograft-bearing mice with NCTD, a CTD analogue with a lower systemic toxicity in vivo, suppressed PP5 activity, increased p-AMPK and reduced tumour volume. Conclusions: Protein phosphatase 5 negatively regulates AMPK phosphorylation and contributes to CCA aggressiveness; thus, PP5 may be a potential therapeutic target in CCA. ? 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
URI: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85057152124&doi=10.1111%2fliv.13887&partnerID=40&md5=82f6768c3dbaf9dfaf671cfdc71e0fd2
https://scholars.lib.ntu.edu.tw/handle/123456789/581824
ISSN: 1478-3223
DOI: 10.1111/liv.13887
SDG/Keyword: cantharidin; caspase 9; cyclin D1; hydroxymethylglutaryl coenzyme A reductase kinase; norcantharidin; phosphoprotein phosphatase; serine threonine protein phosphatase 5; short hairpin RNA; unclassified drug; antineoplastic agent; cantharidin; enzyme inhibitor; hydroxymethylglutaryl coenzyme A reductase kinase; nuclear protein; phosphoprotein phosphatase; protein phosphatase 5; animal cell; animal experiment; animal model; animal tissue; antineoplastic activity; apoptosis; Article; bile duct carcinoma; cancer inhibition; carcinogenesis; cell growth; cell survival; cell viability; colony formation; controlled study; drug targeting; gene knockdown; immunoprecipitation; in vitro study; in vivo study; male; mouse; nonhuman; protein dephosphorylation; protein phosphorylation; tumor volume; tumor xenograft; animal; antagonists and inhibitors; bile duct cancer; bile duct carcinoma; carcinogenesis; cell proliferation; drug screening; genetics; human; knockout mouse; metabolism; nude mouse; pathology; tumor cell line; AMP-Activated Protein Kinases; Animals; Antineoplastic Agents; Apoptosis; Bile Duct Neoplasms; Cantharidin; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cholangiocarcinoma; Enzyme Inhibitors; Humans; Male; Mice; Mice, Knockout; Mice, Nude; Nuclear Proteins; Phosphoprotein Phosphatases; Xenograft Model Antitumor Assays
[SDGs]SDG3
Appears in Collections:臨床醫學研究所

Show full item record

SCOPUSTM   
Citations

5
checked on Mar 13, 2023

WEB OF SCIENCETM
Citations

5
checked on Mar 12, 2023

Page view(s)

33
checked on Mar 24, 2023

Google ScholarTM

Check

Altmetric

Altmetric

Related Items in TAIR


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of “NTU Repository” with “Academic Hub” to form NTU Scholars.

總館學科館員 (Main Library)
醫學圖書館學科館員 (Medical Library)
社會科學院辜振甫紀念圖書館學科館員 (Social Sciences Library)

開放取用是從使用者角度提升資訊取用性的社會運動,應用在學術研究上是透過將研究著作公開供使用者自由取閱,以促進學術傳播及因應期刊訂購費用逐年攀升。同時可加速研究發展、提升研究影響力,NTU Scholars即為本校的開放取用典藏(OA Archive)平台。(點選深入了解OA)

  • 請確認所上傳的全文是原創的內容,若該文件包含部分內容的版權非匯入者所有,或由第三方贊助與合作完成,請確認該版權所有者及第三方同意提供此授權。
    Please represent that the submission is your original work, and that you have the right to grant the rights to upload.
  • 若欲上傳已出版的全文電子檔,可使用Sherpa Romeo網站查詢,以確認出版單位之版權政策。
    Please use Sherpa Romeo to find a summary of permissions that are normally given as part of each publisher's copyright transfer agreement.
  • 網站簡介 (Quickstart Guide)
  • 使用手冊 (Instruction Manual)
  • 線上預約服務 (Booking Service)
  • 方案一:臺灣大學計算機中心帳號登入
    (With C&INC Email Account)
  • 方案二:ORCID帳號登入 (With ORCID)
  • 方案一:定期更新ORCID者,以ID匯入 (Search for identifier (ORCID))
  • 方案二:自行建檔 (Default mode Submission)
  • 方案三:學科館員協助匯入 (Email worklist to subject librarians)
Build with DSpace-CRIS - Extension maintained and optimized by Logo 4SCIENCE Feedback