PMID- 34381712
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210813
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - SIRT1/PGC-1alpha/PPAR-gamma Correlate With Hypoxia-Induced Chemoresistance in Non-Small 
      Cell Lung Cancer.
PG  - 682762
LID - 10.3389/fonc.2021.682762 [doi]
LID - 682762
AB  - Resistance is the major cause of treatment failure and disease progression in 
      non-small cell lung cancer (NSCLC). There is evidence that hypoxia is a key 
      microenvironmental stress associated with resistance to cisplatin, epidermal 
      growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and 
      immunotherapy in solid NSCLCs. Numerous studies have contributed to delineating 
      the mechanisms underlying drug resistance in NSCLC; nevertheless, the mechanisms 
      involved in the resistance associated with hypoxia-induced molecular metabolic 
      adaptations in the microenvironment of NSCLC remain unclear. Studies have 
      highlighted the importance of posttranslational regulation of molecular mediators 
      in the control of mitochondrial function in response to hypoxia-induced metabolic 
      adaptations. Hypoxia can upregulate the expression of sirtuin 1 (SIRT1) in a 
      hypoxia-inducible factor (HIF)-dependent manner. SIRT1 is a stress-dependent 
      metabolic sensor that can deacetylate some key transcriptional factors in both 
      metabolism dependent and independent metabolic pathways such as HIF-1alpha, 
      peroxisome proliferator-activated receptor gamma (PPAR-gamma), and PPAR-gamma 
      coactivator 1-alpha (PGC-1alpha) to affect mitochondrial function and biogenesis, 
      which has a role in hypoxia-induced chemoresistance in NSCLC. Moreover, SIRT1 and 
      HIF-1alpha can regulate both innate and adaptive immune responses through 
      metabolism-dependent and -independent ways. The objective of this review is to 
      delineate a possible SIRT1/PGC-1alpha/PPAR-gamma signaling-related molecular metabolic 
      mechanism underlying hypoxia-induced chemotherapy resistance in the NSCLC 
      microenvironment. Targeting hypoxia-related metabolic adaptation may be an 
      attractive therapeutic strategy for overcoming chemoresistance in NSCLC.
CI  - Copyright (c) 2021 Xu, Luo, Ye, Li, Liu, Du and Zhai.
FAU - Xu, Rui
AU  - Xu R
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Minhang Branch, 
      Shanghai, China.
FAU - Luo, Xin
AU  - Luo X
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Ye, Xuan
AU  - Ye X
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Li, Huan
AU  - Li H
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Liu, Hongyue
AU  - Liu H
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Du, Qiong
AU  - Du Q
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Minhang Branch, 
      Shanghai, China.
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Zhai, Qing
AU  - Zhai Q
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Minhang Branch, 
      Shanghai, China.
AD  - Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210726
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8351465
OTO - NOTNLM
OT  - PGC-1alpha
OT  - PPAR-gamma
OT  - SIRT1
OT  - chemoresistance
OT  - non-small cell lung cancer
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/08/13 06:00
MHDA- 2021/08/13 06:01
PMCR- 2021/01/01
CRDT- 2021/08/12 06:36
PHST- 2021/03/19 00:00 [received]
PHST- 2021/06/30 00:00 [accepted]
PHST- 2021/08/12 06:36 [entrez]
PHST- 2021/08/13 06:00 [pubmed]
PHST- 2021/08/13 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.682762 [doi]
PST - epublish
SO  - Front Oncol. 2021 Jul 26;11:682762. doi: 10.3389/fonc.2021.682762. eCollection 
      2021.