PMID- 28260056
OWN - NLM
STAT- MEDLINE
DCOM- 20170515
LR  - 20220408
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 15
IP  - 4
DP  - 2017 Apr
TI  - Insulin-like growth factor 1 receptor-mediated cell survival in hypoxia depends 
      on the promotion of autophagy via suppression of the PI3K/Akt/mTOR signaling 
      pathway.
PG  - 2136-2142
LID - 10.3892/mmr.2017.6265 [doi]
AB  - Hypoxia is widely accepted as a fundamental biological phenomenon, which is 
      strongly associated with tissue damage and cell viability under stress 
      conditions. Insulin-like growth factor‑1 (IGF‑1) is known to protect tissues from 
      multiple types of damage, and protect cells from apoptosis. Hypoxia is a 
      regulatory factor of the IGF system, however the role of the IGF-1 receptor 
      (IGF‑1R) in hypoxia‑induced apoptosis remains unclear. The present study 
      investigated the potential mechanisms associated with IGF‑1R‑associated apoptosis 
      under hypoxic conditions. Mouse embryonic fibroblasts exhibiting disruption or 
      overexpression of IGF‑1R (R‑ cells and R+ cells) were used to examine the level 
      of apoptosis, autophagy, and production of reactive oxygen species (ROS). The 
      autophagy inhibitor 3‑methyladenine was used to assess the effect of autophagy on 
      ROS production and apoptosis under hypoxic conditions. A potential downstream 
      signaling pathway involving phosphatidylinositol 3-kinase (PI3K)/threonine 
      protein kinase B (Akt)/mammalian target of rapamycin (mTOR) was identifiedby 
      western blot analysis. The results demonstrated that hypoxia induced apoptosis, 
      increased ROS production, and promoted autophagy in a time‑dependent manner 
      relative to that observed under normoxia. R+ cells exhibited a lower percentage 
      of apoptotic cells, lower ROS production, and higher levels of autophagy when 
      compared to that of R- cells. In addition, inhibition of autophagy led to 
      increased ROS production and a higher percentage of apoptotic cells in the two 
      cell types. Furthermore, IGF‑1R is related with PI3K/Akt/mTOR signaling pathway 
      and enhanced autophagy-associated protein expression, which was verified 
      following treatment with the PI3K inhibitor LY294002. These results indicated 
      that IGF‑1R may increase cell viability under hypoxic conditions by promoting 
      autophagy and scavenging ROS production, which is closed with PI3K/Akt/mTOR 
      signaling pathway.
FAU - Liu, Qi
AU  - Liu Q
AD  - Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 
      200032, P.R. China.
FAU - Guan, Jing-Zhi
AU  - Guan JZ
AD  - Department of Oncology, The People's Liberation Army No. 309 Hospital, Beijing 
      100193, P.R. China.
FAU - Sun, Yong
AU  - Sun Y
AD  - Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 
      200032, P.R. China.
FAU - Le, Ziyu
AU  - Le Z
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, P.R. China.
FAU - Zhang, Ping
AU  - Zhang P
AD  - Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 
      200032, P.R. China.
FAU - Yu, Dong
AU  - Yu D
AD  - School of Radiological Medicine and Protection, Medical College of Soochow 
      University, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
FAU - Liu, Yong
AU  - Liu Y
AD  - Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai 
      200032, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170301
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - *Autophagy
MH  - Cell Hypoxia
MH  - Cell Line
MH  - *Cell Survival
MH  - Fibroblasts/cytology/*metabolism
MH  - Hypoxia/*metabolism
MH  - Mice
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Receptor, IGF Type 1/*metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC5364871
EDAT- 2017/03/06 06:00
MHDA- 2017/05/16 06:00
PMCR- 2017/03/01
CRDT- 2017/03/06 06:00
PHST- 2015/12/02 00:00 [received]
PHST- 2016/12/15 00:00 [accepted]
PHST- 2017/03/06 06:00 [pubmed]
PHST- 2017/05/16 06:00 [medline]
PHST- 2017/03/06 06:00 [entrez]
PHST- 2017/03/01 00:00 [pmc-release]
AID - mmr-15-04-2136 [pii]
AID - 10.3892/mmr.2017.6265 [doi]
PST - ppublish
SO  - Mol Med Rep. 2017 Apr;15(4):2136-2142. doi: 10.3892/mmr.2017.6265. Epub 2017 Mar 
      1.