PMID- 29029413
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 39
DP  - 2017 Sep 12
TI  - Targeting SHP-1-STAT3 signaling: A promising therapeutic approach for the 
      treatment of cholangiocarcinoma.
PG  - 65077-65089
LID - 10.18632/oncotarget.17779 [doi]
AB  - 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.
FAU - Hu, Ming-Hung
AU  - Hu MH
AD  - Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan 
      University, Taipei, Taiwan.
AD  - Division of Hematology and Oncology, Department of Medicine, Cardinal Tien 
      Hospital, New Taipei City, Taiwan.
AD  - School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
FAU - Chen, Li-Ju
AU  - Chen LJ
AD  - Department of Medical Research, National Taiwan University Hospital, Taipei, 
      Taiwan.
FAU - Chen, Yen-Lin
AU  - Chen YL
AD  - Department of Pathology, Cardinal Tien Hospital, New Taipei City, Taiwan.
FAU - Tsai, Ming-Shen
AU  - Tsai MS
AD  - Department of Medical Research, National Taiwan University Hospital, Taipei, 
      Taiwan.
FAU - Shiau, Chung-Wai
AU  - Shiau CW
AD  - Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, 
      Taiwan.
FAU - Chao, Tzu-I
AU  - Chao TI
AD  - Transplant Medicine and Surgery Research Centre, Changhua Christian Hospital, 
      Changhua, Taiwan.
FAU - Liu, Chun-Yu
AU  - Liu CY
AD  - Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan.
AD  - School of Medicine, National Yang-Ming University, Taipei, Taiwan.
FAU - Kao, Jia-Horng
AU  - Kao JH
AD  - Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan 
      University, Taipei, Taiwan.
AD  - Division of Gastroenterology and Hepatology, Department of Internal Medicine, 
      National Taiwan University Hospital, Taipei, Taiwan.
FAU - Chen, Kuen-Feng
AU  - Chen KF
AD  - Department of Medical Research, National Taiwan University Hospital, Taipei, 
      Taiwan.
AD  - National Taiwan University College of Medicine, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20170510
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5630313
OTO - NOTNLM
OT  - SC-43
OT  - SHP-1
OT  - STAT3
OT  - cholangiocarcinoma
OT  - inflammatory cancer
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2017/10/17 06:00
MHDA- 2017/10/17 06:01
PMCR- 2017/09/12
CRDT- 2017/10/15 06:00
PHST- 2016/05/09 00:00 [received]
PHST- 2017/04/26 00:00 [accepted]
PHST- 2017/10/15 06:00 [entrez]
PHST- 2017/10/17 06:00 [pubmed]
PHST- 2017/10/17 06:01 [medline]
PHST- 2017/09/12 00:00 [pmc-release]
AID - 17779 [pii]
AID - 10.18632/oncotarget.17779 [doi]
PST - epublish
SO  - Oncotarget. 2017 May 10;8(39):65077-65089. doi: 10.18632/oncotarget.17779. 
      eCollection 2017 Sep 12.