SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer
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...
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.682762/full |
| _version_ | 1818606949998002176 |
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| author | Rui Xu Xin Luo Xin Luo Xuan Ye Xuan Ye Huan Li Huan Li Hongyue Liu Hongyue Liu Qiong Du Qiong Du Qiong Du Qing Zhai Qing Zhai Qing Zhai |
| author_facet | Rui Xu Xin Luo Xin Luo Xuan Ye Xuan Ye Huan Li Huan Li Hongyue Liu Hongyue Liu Qiong Du Qiong Du Qiong Du Qing Zhai Qing Zhai Qing Zhai |
| author_sort | Rui Xu |
| collection | DOAJ |
| description | 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-1α, peroxisome proliferator-activated receptor gamma (PPAR-γ), and PPAR-gamma coactivator 1-alpha (PGC-1α) to affect mitochondrial function and biogenesis, which has a role in hypoxia-induced chemoresistance in NSCLC. Moreover, SIRT1 and HIF-1α 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-1α/PPAR-γ 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. |
| first_indexed | 2024-12-16T14:18:59Z |
| format | Article |
| id | doaj.art-91eaf1748ef84a91865d89092b68df1a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-16T14:18:59Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-91eaf1748ef84a91865d89092b68df1a2022-12-21T22:28:33ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-07-011110.3389/fonc.2021.682762682762SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung CancerRui Xu0Xin Luo1Xin Luo2Xuan Ye3Xuan Ye4Huan Li5Huan Li6Hongyue Liu7Hongyue Liu8Qiong Du9Qiong Du10Qiong Du11Qing Zhai12Qing Zhai13Qing Zhai14Department of Pharmacy, Fudan University Shanghai Cancer Center, Minhang Branch, Shanghai, ChinaDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Minhang Branch, Shanghai, ChinaDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Minhang Branch, Shanghai, ChinaDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaResistance 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-1α, peroxisome proliferator-activated receptor gamma (PPAR-γ), and PPAR-gamma coactivator 1-alpha (PGC-1α) to affect mitochondrial function and biogenesis, which has a role in hypoxia-induced chemoresistance in NSCLC. Moreover, SIRT1 and HIF-1α 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-1α/PPAR-γ 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.682762/fullnon-small cell lung cancerchemoresistanceSIRT1PGC-1αPPAR-γ |
| spellingShingle | Rui Xu Xin Luo Xin Luo Xuan Ye Xuan Ye Huan Li Huan Li Hongyue Liu Hongyue Liu Qiong Du Qiong Du Qiong Du Qing Zhai Qing Zhai Qing Zhai SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer Frontiers in Oncology non-small cell lung cancer chemoresistance SIRT1 PGC-1α PPAR-γ |
| title | SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer |
| title_full | SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer |
| title_fullStr | SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer |
| title_full_unstemmed | SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer |
| title_short | SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer |
| title_sort | sirt1 pgc 1α ppar γ correlate with hypoxia induced chemoresistance in non small cell lung cancer |
| topic | non-small cell lung cancer chemoresistance SIRT1 PGC-1α PPAR-γ |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.682762/full |
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