PMID- 24240056
OWN - NLM
STAT- MEDLINE
DCOM- 20140818
LR  - 20211203
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 26
IP  - 2
DP  - 2014 Feb
TI  - Sustained IRE1 and ATF6 signaling is important for survival of melanoma cells 
      undergoing ER stress.
PG  - 287-94
LID - S0898-6568(13)00329-X [pii]
LID - 10.1016/j.cellsig.2013.11.008 [doi]
AB  - Apoptosis triggered by endoplasmic reticulum (ER) stress is associated with rapid 
      attenuation of the IRE1alpha and ATF6 pathways but persistent activation of the PERK 
      branch of the unfolded protein response (UPR) in cells. However, melanoma cells 
      are largely resistant to ER stress-induced apoptosis, suggesting that the 
      kinetics and durations of activation of the UPR pathways are deregulated in 
      melanoma cells undergoing ER stress. We show here that the IRE1alpha and ATF6 
      pathways are sustained along with the PERK signaling in melanoma cells subjected 
      to pharmacological ER stress, and that this is, at least in part, due to 
      increased activation of the MEK/ERK pathway. In contrast to an initial increase 
      followed by rapid reduction in activation of IRE1alpha and ATF6 signaling in control 
      cells that were relatively sensitive to ER stress-induced apoptosis, activation 
      of IRE1alpha and ATF6 by the pharmacological ER stress inducer tunicamycin (TM) or 
      thapsigargin (TG) persisted in melanoma cells. On the other hand, the increase in 
      PERK signaling lasted similarly in both types of cells. Sustained activation of 
      IRE1alpha and ATF6 signaling played an important role in protecting melanoma cells 
      from ER stress-induced apoptosis, as interruption of IRE1alpha or ATF6 rendered 
      melanoma cells sensitive to apoptosis induced by TM or TG. Inhibition of MEK 
      partially blocked IRE1alpha and ATF6 activation, suggesting that MEK/ERK signaling 
      contributed to sustained activation of IRE1alpha and ATF6. Taken together, these 
      results identify sustained activation of the IRE1alpha and ATF6 pathways of the UPR 
      driven by the MEK/ERK pathway as an important protective mechanism against ER 
      stress-induced apoptosis in melanoma cells.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Tay, Kwang Hong
AU  - Tay KH
AD  - School of Medicine and Public Health, University of Newcastle, NSW 2308, 
      Australia.
FAU - Luan, Qi
AU  - Luan Q
AD  - School of Medicine and Public Health, University of Newcastle, NSW 2308, 
      Australia.
FAU - Croft, Amanda
AU  - Croft A
AD  - School of Medicine and Public Health, University of Newcastle, NSW 2308, 
      Australia; Oncology and Immunology Unit, Calvary Mater Newcastle Mater Hospital, 
      NSW, Australia.
FAU - Jiang, Chen Chen
AU  - Jiang CC
AD  - School of Medicine and Public Health, University of Newcastle, NSW 2308, 
      Australia.
FAU - Jin, Lei
AU  - Jin L
AD  - School of Medicine and Public Health, University of Newcastle, NSW 2308, 
      Australia.
FAU - Zhang, Xu Dong
AU  - Zhang XD
AD  - School of Medicine and Public Health, University of Newcastle, NSW 2308, 
      Australia. Electronic address: Xu.Zhang@newcastle.edu.au.
FAU - Tseng, Hsin-Yi
AU  - Tseng HY
AD  - School of Medicine and Public Health, University of Newcastle, NSW 2308, 
      Australia. Electronic address: Hsin-Yi.Tseng@newcastle.edu.au.
LA  - eng
PT  - Journal Article
DEP - 20131112
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Activating Transcription Factor 6)
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (RNA, Small Interfering)
RN  - 11089-65-9 (Tunicamycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 2.7.11.1 (ERN1 protein, human)
RN  - EC 2.7.11.1 (PERK kinase)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.1.- (Endoribonucleases)
SB  - IM
MH  - Activating Transcription Factor 6/antagonists & inhibitors/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - *Endoplasmic Reticulum Stress/drug effects
MH  - Endoribonucleases/antagonists & inhibitors/genetics/*metabolism
MH  - Eukaryotic Initiation Factor-2/antagonists & inhibitors/genetics/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Melanoma/metabolism/pathology
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/genetics/metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/genetics/metabolism
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/genetics/*metabolism
MH  - RNA, Small Interfering/metabolism
MH  - *Signal Transduction/drug effects
MH  - Thapsigargin/toxicity
MH  - Tunicamycin/toxicity
MH  - Unfolded Protein Response
MH  - eIF-2 Kinase/metabolism
OTO - NOTNLM
OT  - ERK
OT  - Endoplasmic reticulum stress
OT  - Melanoma
OT  - UPR
EDAT- 2013/11/19 06:00
MHDA- 2014/08/19 06:00
CRDT- 2013/11/19 06:00
PHST- 2013/10/22 00:00 [received]
PHST- 2013/11/06 00:00 [accepted]
PHST- 2013/11/19 06:00 [entrez]
PHST- 2013/11/19 06:00 [pubmed]
PHST- 2014/08/19 06:00 [medline]
AID - S0898-6568(13)00329-X [pii]
AID - 10.1016/j.cellsig.2013.11.008 [doi]
PST - ppublish
SO  - Cell Signal. 2014 Feb;26(2):287-94. doi: 10.1016/j.cellsig.2013.11.008. Epub 2013 
      Nov 12.