HIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic Cancer
Pancreatic cancer is intractable due to early progression and resistance to conventional therapy. Dense fibrotic stroma, known as desmoplasia, is a characteristic feature of pancreatic cancer, and develops through the interactions between pancreatic cancer cells and stromal cells, including pancreat...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/2/411 |
| _version_ | 1797495303393247232 |
|---|---|
| author | Shin Hamada Ryotaro Matsumoto Atsushi Masamune |
| author_facet | Shin Hamada Ryotaro Matsumoto Atsushi Masamune |
| author_sort | Shin Hamada |
| collection | DOAJ |
| description | Pancreatic cancer is intractable due to early progression and resistance to conventional therapy. Dense fibrotic stroma, known as desmoplasia, is a characteristic feature of pancreatic cancer, and develops through the interactions between pancreatic cancer cells and stromal cells, including pancreatic stellate cells. Dense stroma forms harsh tumor microenvironments characterized by hypoxia, few nutrients, and oxidative stress. Pancreatic cancer cells as well as pancreatic stellate cells survive in the harsh microenvironments through the altered expression of signaling molecules, transporters, and metabolic enzymes governed by various stress response mechanisms. Hypoxia inducible factor-1 and KEAP1-NRF2, stress response mechanisms for hypoxia and oxidative stress, respectively, contribute to the aggressive behaviors of pancreatic cancer. These key molecules for stress response mechanisms are activated, both in pancreatic cancer cells and in pancreatic stellate cells. Both factors are involved in the mutual activation of cancer cells and stellate cells, by inducing cancer-promoting signals and their mediators. Therapeutic interventions targeting these pathways are promising approaches for novel therapies. In this review, we summarize the roles of stress response mechanisms, focusing on hypoxia inducible factor-1 and KEAP1-NRF2, in pancreatic cancer. In addition, we discuss the potential of targeting these molecules for the treatment of pancreatic cancer. |
| first_indexed | 2024-03-10T01:45:57Z |
| format | Article |
| id | doaj.art-247d085e5d62456da60fea652a15b6c2 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T01:45:57Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-247d085e5d62456da60fea652a15b6c22023-11-23T13:14:31ZengMDPI AGCancers2072-66942022-01-0114241110.3390/cancers14020411HIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic CancerShin Hamada0Ryotaro Matsumoto1Atsushi Masamune2Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanDivision of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai 980-8574, JapanPancreatic cancer is intractable due to early progression and resistance to conventional therapy. Dense fibrotic stroma, known as desmoplasia, is a characteristic feature of pancreatic cancer, and develops through the interactions between pancreatic cancer cells and stromal cells, including pancreatic stellate cells. Dense stroma forms harsh tumor microenvironments characterized by hypoxia, few nutrients, and oxidative stress. Pancreatic cancer cells as well as pancreatic stellate cells survive in the harsh microenvironments through the altered expression of signaling molecules, transporters, and metabolic enzymes governed by various stress response mechanisms. Hypoxia inducible factor-1 and KEAP1-NRF2, stress response mechanisms for hypoxia and oxidative stress, respectively, contribute to the aggressive behaviors of pancreatic cancer. These key molecules for stress response mechanisms are activated, both in pancreatic cancer cells and in pancreatic stellate cells. Both factors are involved in the mutual activation of cancer cells and stellate cells, by inducing cancer-promoting signals and their mediators. Therapeutic interventions targeting these pathways are promising approaches for novel therapies. In this review, we summarize the roles of stress response mechanisms, focusing on hypoxia inducible factor-1 and KEAP1-NRF2, in pancreatic cancer. In addition, we discuss the potential of targeting these molecules for the treatment of pancreatic cancer.https://www.mdpi.com/2072-6694/14/2/411HIF-1KEAP1NRF2hypoxiamicroenvironmentoxidative stress |
| spellingShingle | Shin Hamada Ryotaro Matsumoto Atsushi Masamune HIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic Cancer Cancers HIF-1 KEAP1 NRF2 hypoxia microenvironment oxidative stress |
| title | HIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic Cancer |
| title_full | HIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic Cancer |
| title_fullStr | HIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic Cancer |
| title_full_unstemmed | HIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic Cancer |
| title_short | HIF-1 and NRF2; Key Molecules for Malignant Phenotypes of Pancreatic Cancer |
| title_sort | hif 1 and nrf2 key molecules for malignant phenotypes of pancreatic cancer |
| topic | HIF-1 KEAP1 NRF2 hypoxia microenvironment oxidative stress |
| url | https://www.mdpi.com/2072-6694/14/2/411 |
| work_keys_str_mv | AT shinhamada hif1andnrf2keymoleculesformalignantphenotypesofpancreaticcancer AT ryotaromatsumoto hif1andnrf2keymoleculesformalignantphenotypesofpancreaticcancer AT atsushimasamune hif1andnrf2keymoleculesformalignantphenotypesofpancreaticcancer |