A happy cell stays home: When metabolic stress creates epigenetic advantages in the tumor microenvironment
A paradox of fast-proliferating tumor cells is that they deplete extracellular nutrients that often results in a nutrient poor microenvironment in vivo. Having a better understanding of the adaptation mechanisms cells exhibit in response to metabolic stress will open new therapeutic windows targetin...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.962928/full |
| _version_ | 1818495491849060352 |
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| author | Eric A. Hanse Mei Kong |
| author_facet | Eric A. Hanse Mei Kong |
| author_sort | Eric A. Hanse |
| collection | DOAJ |
| description | A paradox of fast-proliferating tumor cells is that they deplete extracellular nutrients that often results in a nutrient poor microenvironment in vivo. Having a better understanding of the adaptation mechanisms cells exhibit in response to metabolic stress will open new therapeutic windows targeting the tumor’s extreme nutrient microenvironment. Glutamine is one of the most depleted amino acids in the tumor core and here, we provide insight into how important glutamine and its downstream by-product, α-ketoglutarate (αKG), are to communicating information about the nutrient environment. This communication is key in the cell’s ability to foster adaptation. We highlight the epigenetic changes brought on when αKG concentrations are altered in cancer and discuss how depriving cells of glutamine may lead to cancer cell de-differentiation and the ability to grow and thrive in foreign environments. When we starve cells, they adapt to survive. Those survival “skills” allow them to go out looking for other places to live and metastasize. We further examine current challenges to modelling the metabolic tumor microenvironment in the laboratory and discuss strategies that consider current findings to target the tumor’s poor nutrient microenvironment. |
| first_indexed | 2024-12-10T18:21:04Z |
| format | Article |
| id | doaj.art-f9fa6a25e4134d7e90b2af465282d6c3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T18:21:04Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-f9fa6a25e4134d7e90b2af465282d6c32022-12-22T01:38:13ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.962928962928A happy cell stays home: When metabolic stress creates epigenetic advantages in the tumor microenvironmentEric A. HanseMei KongA paradox of fast-proliferating tumor cells is that they deplete extracellular nutrients that often results in a nutrient poor microenvironment in vivo. Having a better understanding of the adaptation mechanisms cells exhibit in response to metabolic stress will open new therapeutic windows targeting the tumor’s extreme nutrient microenvironment. Glutamine is one of the most depleted amino acids in the tumor core and here, we provide insight into how important glutamine and its downstream by-product, α-ketoglutarate (αKG), are to communicating information about the nutrient environment. This communication is key in the cell’s ability to foster adaptation. We highlight the epigenetic changes brought on when αKG concentrations are altered in cancer and discuss how depriving cells of glutamine may lead to cancer cell de-differentiation and the ability to grow and thrive in foreign environments. When we starve cells, they adapt to survive. Those survival “skills” allow them to go out looking for other places to live and metastasize. We further examine current challenges to modelling the metabolic tumor microenvironment in the laboratory and discuss strategies that consider current findings to target the tumor’s poor nutrient microenvironment.https://www.frontiersin.org/articles/10.3389/fonc.2022.962928/fulltumormetabolismglutamineepigeneticsalpha ketoglutarateglutaminolysis-inhibition |
| spellingShingle | Eric A. Hanse Mei Kong A happy cell stays home: When metabolic stress creates epigenetic advantages in the tumor microenvironment Frontiers in Oncology tumor metabolism glutamine epigenetics alpha ketoglutarate glutaminolysis-inhibition |
| title | A happy cell stays home: When metabolic stress creates epigenetic advantages in the tumor microenvironment |
| title_full | A happy cell stays home: When metabolic stress creates epigenetic advantages in the tumor microenvironment |
| title_fullStr | A happy cell stays home: When metabolic stress creates epigenetic advantages in the tumor microenvironment |
| title_full_unstemmed | A happy cell stays home: When metabolic stress creates epigenetic advantages in the tumor microenvironment |
| title_short | A happy cell stays home: When metabolic stress creates epigenetic advantages in the tumor microenvironment |
| title_sort | happy cell stays home when metabolic stress creates epigenetic advantages in the tumor microenvironment |
| topic | tumor metabolism glutamine epigenetics alpha ketoglutarate glutaminolysis-inhibition |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.962928/full |
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