PMID- 31561852
OWN - NLM
STAT- MEDLINE
DCOM- 20200622
LR  - 20200622
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 519
IP  - 4
DP  - 2019 Nov 19
TI  - Farnesoid X receptor induces cell death and sensitizes to TRAIL-induced 
      inhibition of growth in colorectal cancer cells through the up-regulation of 
      death receptor 5.
PG  - 824-831
LID - S0006-291X(19)31754-1 [pii]
LID - 10.1016/j.bbrc.2019.09.033 [doi]
AB  - Farnesoid X receptor (FXR) exhibits critical anti-cancer functions in several 
      types of cancer, including colorectal cancer, in vitro and in vivo. However, the 
      underlying mechanism remains unclear. We evaluated pharmacological activation of 
      FXR with the synthetic agonist GW4064 using comprehensive proteomic analysis in 
      colorectal cancer cell lines (HCT116, SW480, and DLD1). Among the commonly 
      detected proteins in all three cell lines, death receptor 5 (DR5) was the most 
      up-regulated protein, and key autophagy-related proteins, such as 
      microtubule-associated protein 1 light chain 3 alpha/beta (MLP3A/3B) and p62 
      sequestosome-1 (SQSTM), were also differentially expressed. Western blot analysis 
      showed that GW4064 stimulation induced activation of the extrinsic death 
      signaling pathway in all cell lines and induced activation of the intrinsic death 
      signaling pathway in DLD1 cells. Western blotting showed that DR5 up-regulation 
      was associated with inhibition of autophagic activity. These results suggest that 
      FXR activation induced DR5 up-regulation through inhibition of autophagic 
      activity and the DR5-related death signaling pathway. In addition, DR5 selective 
      ligand, also known as TRAIL, has been widely used for anti-cancer treatment in 
      several clinical trials. Co-treatment of TRAIL with GW4064 synergistically 
      inhibited colorectal cancer cell proliferation as compared with single 
      treatments. To the best of our knowledge, our results provide novel insights into 
      FXR function in cancer cell lines. These findings may contribute to a new 
      therapeutic strategy for colorectal cancer.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Hotta, Masahiro
AU  - Hotta M
AD  - Department of Integrated Diagnostic Pathology, Nippon Medical School, 1-1-5 
      Sendagi, Bunkyo-ku, Tokyo, Japan; Department of Gastrointestinal and 
      Hepato-Biliary-Pancreatic Surgery, 1-1-5 Sendagi, Bunkyo-ku, Nippon Medical 
      School, Tokyo, Japan.
FAU - Sakatani, Takashi
AU  - Sakatani T
AD  - Department of Integrated Diagnostic Pathology, Nippon Medical School, 1-1-5 
      Sendagi, Bunkyo-ku, Tokyo, Japan; Department of Diagnostic Pathology, Nippon 
      Medical School Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, Japan. Electronic 
      address: takashi-sakatani@nms.ac.jp.
FAU - Ishino, Kousuke
AU  - Ishino K
AD  - Department of Integrated Diagnostic Pathology, Nippon Medical School, 1-1-5 
      Sendagi, Bunkyo-ku, Tokyo, Japan.
FAU - Wada, Ryuichi
AU  - Wada R
AD  - Department of Integrated Diagnostic Pathology, Nippon Medical School, 1-1-5 
      Sendagi, Bunkyo-ku, Tokyo, Japan.
FAU - Kudo, Mitsuhiro
AU  - Kudo M
AD  - Department of Integrated Diagnostic Pathology, Nippon Medical School, 1-1-5 
      Sendagi, Bunkyo-ku, Tokyo, Japan.
FAU - Yokoyama, Yasuyuki
AU  - Yokoyama Y
AD  - Department of Integrated Diagnostic Pathology, Nippon Medical School, 1-1-5 
      Sendagi, Bunkyo-ku, Tokyo, Japan; Department of Gastrointestinal and 
      Hepato-Biliary-Pancreatic Surgery, 1-1-5 Sendagi, Bunkyo-ku, Nippon Medical 
      School, Tokyo, Japan.
FAU - Yamada, Takeshi
AU  - Yamada T
AD  - Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, 1-1-5 
      Sendagi, Bunkyo-ku, Nippon Medical School, Tokyo, Japan.
FAU - Yoshida, Hiroshi
AU  - Yoshida H
AD  - Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, 1-1-5 
      Sendagi, Bunkyo-ku, Nippon Medical School, Tokyo, Japan.
FAU - Naito, Zenya
AU  - Naito Z
AD  - Department of Integrated Diagnostic Pathology, Nippon Medical School, 1-1-5 
      Sendagi, Bunkyo-ku, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20190924
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Isoxazoles)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (SQSTM1 protein, human)
RN  - 0 (Sequestosome-1 Protein)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0C5V0MRU6P (farnesoid X-activated receptor)
RN  - SR225WUZ0H (GW 4064)
SB  - IM
MH  - Autophagy/*drug effects/genetics
MH  - Cell Death/drug effects/genetics
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects/genetics
MH  - Colorectal Neoplasms/genetics/metabolism/pathology
MH  - HCT116 Cells
MH  - Humans
MH  - Isoxazoles/*pharmacology
MH  - Proteomics/methods
MH  - Receptors, Cytoplasmic and Nuclear/*agonists/genetics/metabolism
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics/*metabolism
MH  - Sequestosome-1 Protein/genetics/*metabolism
MH  - Signal Transduction/drug effects/genetics
MH  - TNF-Related Apoptosis-Inducing Ligand/*pharmacology
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - Autophagy
OT  - Colorectal cancer
OT  - Death receptor 5
OT  - Farnesoid X receptor
OT  - Proteomics
OT  - TRAIL
EDAT- 2019/09/29 06:00
MHDA- 2020/06/23 06:00
CRDT- 2019/09/29 06:00
PHST- 2019/08/30 00:00 [received]
PHST- 2019/09/09 00:00 [accepted]
PHST- 2019/09/29 06:00 [pubmed]
PHST- 2020/06/23 06:00 [medline]
PHST- 2019/09/29 06:00 [entrez]
AID - S0006-291X(19)31754-1 [pii]
AID - 10.1016/j.bbrc.2019.09.033 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Nov 19;519(4):824-831. doi: 
      10.1016/j.bbrc.2019.09.033. Epub 2019 Sep 24.