Targeting Mitochondrial OXPHOS and Their Regulatory Signals in Prostate Cancers
Increasing evidence suggests that tumor development requires not only oncogene/tumor suppressor mutations to drive the growth, survival, and metastasis but also metabolic adaptations to meet the increasing energy demand for rapid cellular expansion and to cope with the often nutritional and oxygen-d...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/24/13435 |
| _version_ | 1797503833202491392 |
|---|---|
| author | Chia-Lin Chen Ching-Yu Lin Hsing-Jien Kung |
| author_facet | Chia-Lin Chen Ching-Yu Lin Hsing-Jien Kung |
| author_sort | Chia-Lin Chen |
| collection | DOAJ |
| description | Increasing evidence suggests that tumor development requires not only oncogene/tumor suppressor mutations to drive the growth, survival, and metastasis but also metabolic adaptations to meet the increasing energy demand for rapid cellular expansion and to cope with the often nutritional and oxygen-deprived microenvironment. One well-recognized strategy is to shift the metabolic flow from oxidative phosphorylation (OXPHOS) or respiration in mitochondria to glycolysis or fermentation in cytosol, known as Warburg effects. However, not all cancer cells follow this paradigm. In the development of prostate cancer, OXPHOS actually increases as compared to normal prostate tissue. This is because normal prostate epithelial cells divert citrate in mitochondria for the TCA cycle to the cytosol for secretion into seminal fluid. The sustained level of OXPHOS in primary tumors persists in progression to an advanced stage. As such, targeting OXPHOS and mitochondrial activities in general present therapeutic opportunities. In this review, we summarize the recent findings of the key regulators of the OXPHOS pathway in prostate cancer, ranging from transcriptional regulation, metabolic regulation to genetic regulation. Moreover, we provided a comprehensive update of the current status of OXPHOS inhibitors for prostate cancer therapy. A challenge of developing OXPHOS inhibitors is to selectively target cancer mitochondria and spare normal counterparts, which is also discussed. |
| first_indexed | 2024-03-10T03:56:00Z |
| format | Article |
| id | doaj.art-d9d91f676388419db66be602bbf7d7aa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:56:00Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d9d91f676388419db66be602bbf7d7aa2023-11-23T08:46:16ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241343510.3390/ijms222413435Targeting Mitochondrial OXPHOS and Their Regulatory Signals in Prostate CancersChia-Lin Chen0Ching-Yu Lin1Hsing-Jien Kung2Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, TaiwanPh.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, TaiwanPh.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, TaiwanIncreasing evidence suggests that tumor development requires not only oncogene/tumor suppressor mutations to drive the growth, survival, and metastasis but also metabolic adaptations to meet the increasing energy demand for rapid cellular expansion and to cope with the often nutritional and oxygen-deprived microenvironment. One well-recognized strategy is to shift the metabolic flow from oxidative phosphorylation (OXPHOS) or respiration in mitochondria to glycolysis or fermentation in cytosol, known as Warburg effects. However, not all cancer cells follow this paradigm. In the development of prostate cancer, OXPHOS actually increases as compared to normal prostate tissue. This is because normal prostate epithelial cells divert citrate in mitochondria for the TCA cycle to the cytosol for secretion into seminal fluid. The sustained level of OXPHOS in primary tumors persists in progression to an advanced stage. As such, targeting OXPHOS and mitochondrial activities in general present therapeutic opportunities. In this review, we summarize the recent findings of the key regulators of the OXPHOS pathway in prostate cancer, ranging from transcriptional regulation, metabolic regulation to genetic regulation. Moreover, we provided a comprehensive update of the current status of OXPHOS inhibitors for prostate cancer therapy. A challenge of developing OXPHOS inhibitors is to selectively target cancer mitochondria and spare normal counterparts, which is also discussed.https://www.mdpi.com/1422-0067/22/24/13435mitochondriaOXPHOScancer therapy |
| spellingShingle | Chia-Lin Chen Ching-Yu Lin Hsing-Jien Kung Targeting Mitochondrial OXPHOS and Their Regulatory Signals in Prostate Cancers International Journal of Molecular Sciences mitochondria OXPHOS cancer therapy |
| title | Targeting Mitochondrial OXPHOS and Their Regulatory Signals in Prostate Cancers |
| title_full | Targeting Mitochondrial OXPHOS and Their Regulatory Signals in Prostate Cancers |
| title_fullStr | Targeting Mitochondrial OXPHOS and Their Regulatory Signals in Prostate Cancers |
| title_full_unstemmed | Targeting Mitochondrial OXPHOS and Their Regulatory Signals in Prostate Cancers |
| title_short | Targeting Mitochondrial OXPHOS and Their Regulatory Signals in Prostate Cancers |
| title_sort | targeting mitochondrial oxphos and their regulatory signals in prostate cancers |
| topic | mitochondria OXPHOS cancer therapy |
| url | https://www.mdpi.com/1422-0067/22/24/13435 |
| work_keys_str_mv | AT chialinchen targetingmitochondrialoxphosandtheirregulatorysignalsinprostatecancers AT chingyulin targetingmitochondrialoxphosandtheirregulatorysignalsinprostatecancers AT hsingjienkung targetingmitochondrialoxphosandtheirregulatorysignalsinprostatecancers |