How protons pave the way to aggressive cancers
Cancers undergo sequential changes to proton (H+) concentration and sensing that are consequences of the disease and facilitate its further progression. The impact of protonation state on protein activity can arise from alterations to amino acids or their titration. Indeed, many cancer-initiating mu...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2023
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| _version_ | 1826312897692696576 |
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| author | Swietach, P Boedtkjer, E Pedersen, SF |
| author_facet | Swietach, P Boedtkjer, E Pedersen, SF |
| author_sort | Swietach, P |
| collection | OXFORD |
| description | Cancers undergo sequential changes to proton (H+) concentration and sensing that are consequences of the disease and facilitate its further progression. The impact of protonation state on protein activity can arise from alterations to amino acids or their titration. Indeed, many cancer-initiating mutations influence pH balance, regulation or sensing in a manner that enables growth and invasion outside normal constraints as part of oncogenic transformation. These cancer-supporting effects become more prominent when tumours develop an acidic microenvironment owing to metabolic reprogramming and disordered perfusion. The ensuing intracellular and extracellular pH disturbances affect multiple aspects of tumour biology, ranging from proliferation to immune surveillance, and can even facilitate further mutagenesis. As a selection pressure, extracellular acidosis accelerates disease progression by favouring acid-resistant cancer cells, which are typically associated with aggressive phenotypes. Although acid–base disturbances in tumours often occur alongside hypoxia and lactate accumulation, there is now ample evidence for a distinct role of H+-operated responses in key events underpinning cancer. The breadth of these actions presents therapeutic opportunities to change the trajectory of disease. |
| first_indexed | 2024-03-07T08:08:39Z |
| format | Journal article |
| id | oxford-uuid:c645350e-f545-42fb-b38d-12af9f63a494 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:02:22Z |
| publishDate | 2023 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:c645350e-f545-42fb-b38d-12af9f63a4942024-04-26T10:47:58ZHow protons pave the way to aggressive cancersJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c645350e-f545-42fb-b38d-12af9f63a494EnglishSymplectic ElementsSpringer Nature2023Swietach, PBoedtkjer, EPedersen, SFCancers undergo sequential changes to proton (H+) concentration and sensing that are consequences of the disease and facilitate its further progression. The impact of protonation state on protein activity can arise from alterations to amino acids or their titration. Indeed, many cancer-initiating mutations influence pH balance, regulation or sensing in a manner that enables growth and invasion outside normal constraints as part of oncogenic transformation. These cancer-supporting effects become more prominent when tumours develop an acidic microenvironment owing to metabolic reprogramming and disordered perfusion. The ensuing intracellular and extracellular pH disturbances affect multiple aspects of tumour biology, ranging from proliferation to immune surveillance, and can even facilitate further mutagenesis. As a selection pressure, extracellular acidosis accelerates disease progression by favouring acid-resistant cancer cells, which are typically associated with aggressive phenotypes. Although acid–base disturbances in tumours often occur alongside hypoxia and lactate accumulation, there is now ample evidence for a distinct role of H+-operated responses in key events underpinning cancer. The breadth of these actions presents therapeutic opportunities to change the trajectory of disease. |
| spellingShingle | Swietach, P Boedtkjer, E Pedersen, SF How protons pave the way to aggressive cancers |
| title | How protons pave the way to aggressive cancers |
| title_full | How protons pave the way to aggressive cancers |
| title_fullStr | How protons pave the way to aggressive cancers |
| title_full_unstemmed | How protons pave the way to aggressive cancers |
| title_short | How protons pave the way to aggressive cancers |
| title_sort | how protons pave the way to aggressive cancers |
| work_keys_str_mv | AT swietachp howprotonspavethewaytoaggressivecancers AT boedtkjere howprotonspavethewaytoaggressivecancers AT pedersensf howprotonspavethewaytoaggressivecancers |