New Discoveries and Ambiguities of Nrf2 and ATF3 Signaling in Environmental Arsenic-Induced Carcinogenesis
Environment exposure to arsenic had been linked to increased incidents of human cancers. In cellular and animal experimental systems, arsenic has been shown to be highly capable of activating several signaling pathways that play critical roles in cell growth regulation, malignant transformation and...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/11/1/77 |
| _version_ | 1797496241176707072 |
|---|---|
| author | Zhuoyue Bi Yao Fu Priya Wadgaonkar Yiran Qiu Bandar Almutairy Wenxuan Zhang Akimasa Seno Chitra Thakur Fei Chen |
| author_facet | Zhuoyue Bi Yao Fu Priya Wadgaonkar Yiran Qiu Bandar Almutairy Wenxuan Zhang Akimasa Seno Chitra Thakur Fei Chen |
| author_sort | Zhuoyue Bi |
| collection | DOAJ |
| description | Environment exposure to arsenic had been linked to increased incidents of human cancers. In cellular and animal experimental systems, arsenic has been shown to be highly capable of activating several signaling pathways that play critical roles in cell growth regulation, malignant transformation and the stemness of cancer stem-like cells. Emerging evidence indicates certain oncogenic properties of the Nrf2 transcription factor that can be activated by arsenic and many other environmental hazards. In human bronchial epithelial cells, our most recent data suggested that arsenic-activated Nrf2 signaling fosters metabolic reprogramming of the cells through shifting mitochondrial TCA cycle to cytosolic glycolysis, and some of the metabolites in glycolysis shunt the hexosamine biosynthesis and serine-glycine pathways important for the energy metabolism of the cancer cells. In the current report, we further demonstrated direct regulation of oncogenic signals by arsenic-activated Nrf2 and connection of Nrf2 with ATF3 stress transcription factor. Meanwhile, we also highlighted some unanswered questions on the molecular characteristics of the Nrf2 protein, which warrants further collaborative efforts among scientists for understanding the important role of Nrf2 in human cancers either associated or not to environmental arsenic exposure. |
| first_indexed | 2024-03-10T03:00:50Z |
| format | Article |
| id | doaj.art-74891d3e3dfa4e97b7efe7f084b2b0a1 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T03:00:50Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-74891d3e3dfa4e97b7efe7f084b2b0a12023-11-23T12:46:58ZengMDPI AGAntioxidants2076-39212021-12-011117710.3390/antiox11010077New Discoveries and Ambiguities of Nrf2 and ATF3 Signaling in Environmental Arsenic-Induced CarcinogenesisZhuoyue Bi0Yao Fu1Priya Wadgaonkar2Yiran Qiu3Bandar Almutairy4Wenxuan Zhang5Akimasa Seno6Chitra Thakur7Fei Chen8Stony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Brookhaven, NY 11794, USAStony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Brookhaven, NY 11794, USADepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USAStony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Brookhaven, NY 11794, USADepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USAStony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Brookhaven, NY 11794, USADepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USAStony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Brookhaven, NY 11794, USAStony Brook Cancer Center, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Brookhaven, NY 11794, USAEnvironment exposure to arsenic had been linked to increased incidents of human cancers. In cellular and animal experimental systems, arsenic has been shown to be highly capable of activating several signaling pathways that play critical roles in cell growth regulation, malignant transformation and the stemness of cancer stem-like cells. Emerging evidence indicates certain oncogenic properties of the Nrf2 transcription factor that can be activated by arsenic and many other environmental hazards. In human bronchial epithelial cells, our most recent data suggested that arsenic-activated Nrf2 signaling fosters metabolic reprogramming of the cells through shifting mitochondrial TCA cycle to cytosolic glycolysis, and some of the metabolites in glycolysis shunt the hexosamine biosynthesis and serine-glycine pathways important for the energy metabolism of the cancer cells. In the current report, we further demonstrated direct regulation of oncogenic signals by arsenic-activated Nrf2 and connection of Nrf2 with ATF3 stress transcription factor. Meanwhile, we also highlighted some unanswered questions on the molecular characteristics of the Nrf2 protein, which warrants further collaborative efforts among scientists for understanding the important role of Nrf2 in human cancers either associated or not to environmental arsenic exposure.https://www.mdpi.com/2076-3921/11/1/77arsenicNrf2carcinogenesisATF3ChIP-seq |
| spellingShingle | Zhuoyue Bi Yao Fu Priya Wadgaonkar Yiran Qiu Bandar Almutairy Wenxuan Zhang Akimasa Seno Chitra Thakur Fei Chen New Discoveries and Ambiguities of Nrf2 and ATF3 Signaling in Environmental Arsenic-Induced Carcinogenesis Antioxidants arsenic Nrf2 carcinogenesis ATF3 ChIP-seq |
| title | New Discoveries and Ambiguities of Nrf2 and ATF3 Signaling in Environmental Arsenic-Induced Carcinogenesis |
| title_full | New Discoveries and Ambiguities of Nrf2 and ATF3 Signaling in Environmental Arsenic-Induced Carcinogenesis |
| title_fullStr | New Discoveries and Ambiguities of Nrf2 and ATF3 Signaling in Environmental Arsenic-Induced Carcinogenesis |
| title_full_unstemmed | New Discoveries and Ambiguities of Nrf2 and ATF3 Signaling in Environmental Arsenic-Induced Carcinogenesis |
| title_short | New Discoveries and Ambiguities of Nrf2 and ATF3 Signaling in Environmental Arsenic-Induced Carcinogenesis |
| title_sort | new discoveries and ambiguities of nrf2 and atf3 signaling in environmental arsenic induced carcinogenesis |
| topic | arsenic Nrf2 carcinogenesis ATF3 ChIP-seq |
| url | https://www.mdpi.com/2076-3921/11/1/77 |
| work_keys_str_mv | AT zhuoyuebi newdiscoveriesandambiguitiesofnrf2andatf3signalinginenvironmentalarsenicinducedcarcinogenesis AT yaofu newdiscoveriesandambiguitiesofnrf2andatf3signalinginenvironmentalarsenicinducedcarcinogenesis AT priyawadgaonkar newdiscoveriesandambiguitiesofnrf2andatf3signalinginenvironmentalarsenicinducedcarcinogenesis AT yiranqiu newdiscoveriesandambiguitiesofnrf2andatf3signalinginenvironmentalarsenicinducedcarcinogenesis AT bandaralmutairy newdiscoveriesandambiguitiesofnrf2andatf3signalinginenvironmentalarsenicinducedcarcinogenesis AT wenxuanzhang newdiscoveriesandambiguitiesofnrf2andatf3signalinginenvironmentalarsenicinducedcarcinogenesis AT akimasaseno newdiscoveriesandambiguitiesofnrf2andatf3signalinginenvironmentalarsenicinducedcarcinogenesis AT chitrathakur newdiscoveriesandambiguitiesofnrf2andatf3signalinginenvironmentalarsenicinducedcarcinogenesis AT feichen newdiscoveriesandambiguitiesofnrf2andatf3signalinginenvironmentalarsenicinducedcarcinogenesis |