Interplay between sirtuins, MYC and hypoxia-inducible factor in cancer-associated metabolic reprogramming
In the early twentieth century, Otto Heinrich Warburg described an elevated rate of glycolysis occurring in cancer cells, even in the presence of atmospheric oxygen (the Warburg effect). Despite the inefficiency of ATP generation through glycolysis, the breakdown of glucose into lactate provides can...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2014-09-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/7/9/1023 |
| _version_ | 1828522376021671936 |
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| author | Bernadette M. M. Zwaans David B. Lombard |
| author_facet | Bernadette M. M. Zwaans David B. Lombard |
| author_sort | Bernadette M. M. Zwaans |
| collection | DOAJ |
| description | In the early twentieth century, Otto Heinrich Warburg described an elevated rate of glycolysis occurring in cancer cells, even in the presence of atmospheric oxygen (the Warburg effect). Despite the inefficiency of ATP generation through glycolysis, the breakdown of glucose into lactate provides cancer cells with a number of advantages, including the ability to withstand fluctuations in oxygen levels, and the production of intermediates that serve as building blocks to support rapid proliferation. Recent evidence from many cancer types supports the notion that pervasive metabolic reprogramming in cancer and stromal cells is a crucial feature of neoplastic transformation. Two key transcription factors that play major roles in this metabolic reprogramming are hypoxia inducible factor-1 (HIF1) and MYC. Sirtuin-family deacetylases regulate diverse biological processes, including many aspects of tumor biology. Recently, the sirtuin SIRT6 has been shown to inhibit the transcriptional output of both HIF1 and MYC, and to function as a tumor suppressor. In this Review, we highlight the importance of HIF1 and MYC in regulating tumor metabolism and their regulation by sirtuins, with a main focus on SIRT6. |
| first_indexed | 2024-12-11T20:06:38Z |
| format | Article |
| id | doaj.art-2bfc1596067f498b85709eba22e7da76 |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-11T20:06:38Z |
| publishDate | 2014-09-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-2bfc1596067f498b85709eba22e7da762022-12-22T00:52:23ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112014-09-01791023103210.1242/dmm.016287016287Interplay between sirtuins, MYC and hypoxia-inducible factor in cancer-associated metabolic reprogrammingBernadette M. M. ZwaansDavid B. LombardIn the early twentieth century, Otto Heinrich Warburg described an elevated rate of glycolysis occurring in cancer cells, even in the presence of atmospheric oxygen (the Warburg effect). Despite the inefficiency of ATP generation through glycolysis, the breakdown of glucose into lactate provides cancer cells with a number of advantages, including the ability to withstand fluctuations in oxygen levels, and the production of intermediates that serve as building blocks to support rapid proliferation. Recent evidence from many cancer types supports the notion that pervasive metabolic reprogramming in cancer and stromal cells is a crucial feature of neoplastic transformation. Two key transcription factors that play major roles in this metabolic reprogramming are hypoxia inducible factor-1 (HIF1) and MYC. Sirtuin-family deacetylases regulate diverse biological processes, including many aspects of tumor biology. Recently, the sirtuin SIRT6 has been shown to inhibit the transcriptional output of both HIF1 and MYC, and to function as a tumor suppressor. In this Review, we highlight the importance of HIF1 and MYC in regulating tumor metabolism and their regulation by sirtuins, with a main focus on SIRT6.http://dmm.biologists.org/content/7/9/1023SirtuinsMYCHIFWarburg effectMetabolic reprogramming |
| spellingShingle | Bernadette M. M. Zwaans David B. Lombard Interplay between sirtuins, MYC and hypoxia-inducible factor in cancer-associated metabolic reprogramming Disease Models & Mechanisms Sirtuins MYC HIF Warburg effect Metabolic reprogramming |
| title | Interplay between sirtuins, MYC and hypoxia-inducible factor in cancer-associated metabolic reprogramming |
| title_full | Interplay between sirtuins, MYC and hypoxia-inducible factor in cancer-associated metabolic reprogramming |
| title_fullStr | Interplay between sirtuins, MYC and hypoxia-inducible factor in cancer-associated metabolic reprogramming |
| title_full_unstemmed | Interplay between sirtuins, MYC and hypoxia-inducible factor in cancer-associated metabolic reprogramming |
| title_short | Interplay between sirtuins, MYC and hypoxia-inducible factor in cancer-associated metabolic reprogramming |
| title_sort | interplay between sirtuins myc and hypoxia inducible factor in cancer associated metabolic reprogramming |
| topic | Sirtuins MYC HIF Warburg effect Metabolic reprogramming |
| url | http://dmm.biologists.org/content/7/9/1023 |
| work_keys_str_mv | AT bernadettemmzwaans interplaybetweensirtuinsmycandhypoxiainduciblefactorincancerassociatedmetabolicreprogramming AT davidblombard interplaybetweensirtuinsmycandhypoxiainduciblefactorincancerassociatedmetabolicreprogramming |