PMID- 28867195
OWN - NLM
STAT- MEDLINE
DCOM- 20171023
LR  - 20191210
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 493
IP  - 1
DP  - 2017 Nov 4
TI  - Simultaneous targeting PI3K and PERK pathways promotes cell death and improves 
      the clinical prognosis in esophageal squamous carcinoma.
PG  - 534-541
LID - S0006-291X(17)31730-8 [pii]
LID - 10.1016/j.bbrc.2017.08.156 [doi]
AB  - PI3K pathway is an important anti-tumor target, but its effect and mechanism is 
      not clear in esophageal squamous cell carcinoma (ESCC). By analysis of the Cancer 
      Genome Atlas (TCGA) datasets, we found that PI3Ks level were significantly 
      upregulated in human esophageal cancer tissues compared with that in non-cancer 
      tissues. The alteration of PI3K can significantly affect the overall patient 
      survival in ESCC but not in esophageal adenocarcinoma (EAC). We found that the 
      classic PI3K inhibitor LY294002 obviously inhibited the canonical mammalian 
      target of rapamycin (mTOR) pathway and restrained the growth of ESCC with less 
      toxicity to normal cells. Besides, LY294002 inhibited noncanonical PKR-like ER 
      kinase (PERK)/elF2alpha/ATF4 pathway as well. Both siRNA and the small molecule 
      inhibitor GSK2656157 against PERK/elF2alpha/ATF4 pathway can significantly inhibit 
      the growth of ESCC. More importantly, GSK2656157 aggravated the inhibitory effect 
      of LY294002 on cell growth, colony formation, and apoptosis induction of ESCC. In 
      addition of dual high expression of PI3K and PERK pathways in the ESCC patients, 
      the difference of overall survival (OS) was more significant than using PI3K 
      alone. These results indicated that dual targeting of PI3K and PERK pathways 
      might improve clinical prognosis and enhance the treatment of ESCC patients.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Wang, Shao-Qi
AU  - Wang SQ
AD  - Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study 
      Center, Zhongnan Hospital, Wuhan University, Wuhan, China; Department of 
      Radiation Oncology and Medical Oncology, Zhongnan Hospital, Wuhan University, 
      Wuhan, China.
FAU - Wang, Xiao
AU  - Wang X
AD  - Department of Pharmacy, Shenzhen People's Hospital, The Second Clinical Medical 
      College of Jinan University, Shenzhen, China.
FAU - Zheng, Kai
AU  - Zheng K
AD  - Department of Medicine, Shenzhen University, Shenzhen, China.
FAU - Liu, Kai-Sheng
AU  - Liu KS
AD  - Department of Pharmacy, Shenzhen People's Hospital, The Second Clinical Medical 
      College of Jinan University, Shenzhen, China.
FAU - Wang, Shao-Xiang
AU  - Wang SX
AD  - Department of Medicine, Shenzhen University, Shenzhen, China. Electronic address: 
      wsx@szu.edu.cn.
FAU - Xie, Cong-Hua
AU  - Xie CH
AD  - Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study 
      Center, Zhongnan Hospital, Wuhan University, Wuhan, China; Department of 
      Radiation Oncology and Medical Oncology, Zhongnan Hospital, Wuhan University, 
      Wuhan, China. Electronic address: chxie_65@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20170901
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Antineoplastic Agents)
RN  - 0 (GSK2656157)
RN  - 0 (Indoles)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - EC 2.7.11.1 (EIF2AK3 protein, human)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - JAC85A2161 (Adenine)
SB  - IM
MH  - Adenine/administration & dosage/*analogs & derivatives
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage
MH  - Apoptosis/*drug effects
MH  - Carcinoma, Squamous Cell/*drug therapy/*metabolism/mortality
MH  - China/epidemiology
MH  - Esophageal Neoplasms/*drug therapy/*metabolism/mortality
MH  - Esophageal Squamous Cell Carcinoma
MH  - Female
MH  - Humans
MH  - Indoles/*administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Prevalence
MH  - Prognosis
MH  - Signal Transduction/*drug effects
MH  - Survival Rate
MH  - Treatment Outcome
MH  - eIF-2 Kinase/antagonists & inhibitors/*metabolism
OTO - NOTNLM
OT  - ESCC
OT  - GSK2656157
OT  - LY294002
OT  - PERK
OT  - PI3K
OT  - mTOR
EDAT- 2017/09/05 06:00
MHDA- 2017/10/24 06:00
CRDT- 2017/09/05 06:00
PHST- 2017/08/25 00:00 [received]
PHST- 2017/08/31 00:00 [accepted]
PHST- 2017/09/05 06:00 [pubmed]
PHST- 2017/10/24 06:00 [medline]
PHST- 2017/09/05 06:00 [entrez]
AID - S0006-291X(17)31730-8 [pii]
AID - 10.1016/j.bbrc.2017.08.156 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2017 Nov 4;493(1):534-541. doi: 
      10.1016/j.bbrc.2017.08.156. Epub 2017 Sep 1.