PMID- 27530187
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20211204
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 64
IP  - 5
DP  - 2016 Nov
TI  - Angiopoietin-like protein 1 antagonizes MET receptor activity to repress 
      sorafenib resistance and cancer stemness in hepatocellular carcinoma.
PG  - 1637-1651
LID - 10.1002/hep.28773 [doi]
AB  - Angiopoietin-like protein 1 (ANGPTL1) has been shown to act as a tumor suppressor 
      by inhibiting angiogenesis, cancer invasion, and metastasis. However, little is 
      known about the effects of ANGPTL1 on sorafenib resistance and cancer stem cell 
      properties in hepatocellular carcinoma (HCC) and the mechanism underlying these 
      effects. Here, we show that ANGPTL1 expression positively correlates with 
      sorafenib sensitivity in HCC cells and human HCC tissues. ANGPTL1 significantly 
      decreases epithelial-mesenchymal transition (EMT)-driven sorafenib resistance, 
      cancer stemness, and tumor growth of HCC cells by repressing Slug expression. 
      ANGPTL1 directly interacts with and inactivates MET receptor, which contributes 
      to Slug suppression through inhibition of the extracellular receptor 
      kinase/protein kinase B (ERK/AKT)-dependent early growth response protein 1 
      (Egr-1) pathway. ANGPTL1 expression inversely correlates with Slug expression, 
      poor sorafenib responsiveness, and poor clinical outcomes in HCC patients. 
      CONCLUSION: ANGPTL1 inhibits sorafenib resistance and cancer stemness in HCC 
      cells by repressing EMT through inhibition of the MET receptor-AKT/ERK-Egr-1-Slug 
      signaling cascade. ANGPTL1 may serve as a novel MET receptor inhibitor for 
      advanced HCC therapy. (Hepatology 2016;64:1637-1651).
CI  - (c) 2016 by the American Association for the Study of Liver Diseases.
FAU - Chen, Hsin-An
AU  - Chen HA
AD  - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical 
      University, Taipei, Taiwan.
AD  - Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei 
      Medical University, New Taipei City, Taiwan.
AD  - Division of General Surgery, Department of Surgery, School of Medicine, College 
      of Medicine, Taipei Medical University, Taipei, Taiwan.
FAU - Kuo, Tsang-Chih
AU  - Kuo TC
AD  - Institute of Biochemical Sciences, College of Life Science, National Taiwan 
      University, Taipei, Taiwan.
FAU - Tseng, Chi-Feng
AU  - Tseng CF
AD  - National Institute of Cancer Research, National Health Research Institutes, 
      Zhunan, Taiwan.
AD  - Graduate Program of Biotechnology in Medicine College of Life Science, National 
      Tsing Hua University, Hsinchu, Taiwan.
FAU - Ma, Jui-Ti
AU  - Ma JT
AD  - National Institute of Cancer Research, National Health Research Institutes, 
      Zhunan, Taiwan.
FAU - Yang, Shu-Ting
AU  - Yang ST
AD  - National Institute of Cancer Research, National Health Research Institutes, 
      Zhunan, Taiwan.
FAU - Yen, Chia-Jui
AU  - Yen CJ
AD  - Division of Hematology-Oncology, Department of Internal Medicine, National Cheng 
      Kung University Hospital, Tainan, Taiwan.
FAU - Yang, Ching-Yao
AU  - Yang CY
AD  - Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
FAU - Sung, Shian-Ying
AU  - Sung SY
AD  - Program for Translational Medicine, College of Medical Science and Technology, 
      Taipei Medical University, Taipei, Taiwan.
FAU - Su, Jen-Liang
AU  - Su JL
AD  - National Institute of Cancer Research, National Health Research Institutes, 
      Zhunan, Taiwan. jlsu@nhri.org.tw.
AD  - Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 
      Taiwan. jlsu@nhri.org.tw.
AD  - Center for Molecular Medicine, China Medical University Hospital, Taichung, 
      Taiwan. jlsu@nhri.org.tw.
AD  - Department of Biotechnology, Asia University, Taichung, Taiwan. jlsu@nhri.org.tw.
LA  - eng
PT  - Journal Article
DEP - 20160923
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (ANGPTL1 protein, human)
RN  - 0 (Angiopoietin-Like Protein 1)
RN  - 0 (Angiopoietin-like Proteins)
RN  - 0 (Angiopoietins)
RN  - 0 (Angptl1 protein, mouse)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phenylurea Compounds)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
EIN - Hepatology. 2017 Feb;65(2):760. PMID: 28114740
MH  - Angiopoietin-Like Protein 1
MH  - Angiopoietin-like Proteins
MH  - Angiopoietins/*physiology
MH  - Animals
MH  - Antineoplastic Agents/*therapeutic use
MH  - Carcinoma, Hepatocellular/*drug therapy
MH  - *Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Liver Neoplasms/*drug therapy
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Neoplastic Stem Cells
MH  - Niacinamide/*analogs & derivatives/therapeutic use
MH  - Phenylurea Compounds/*therapeutic use
MH  - Proto-Oncogene Proteins c-met/*physiology
MH  - Sorafenib
EDAT- 2016/10/22 06:00
MHDA- 2017/08/02 06:00
CRDT- 2016/08/18 06:00
PHST- 2016/03/03 00:00 [received]
PHST- 2016/07/21 00:00 [accepted]
PHST- 2016/10/22 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
PHST- 2016/08/18 06:00 [entrez]
AID - 10.1002/hep.28773 [doi]
PST - ppublish
SO  - Hepatology. 2016 Nov;64(5):1637-1651. doi: 10.1002/hep.28773. Epub 2016 Sep 23.