Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers
Cobalamin or vitamin B12 (B12) is a cofactor for methionine synthase and methylmalonyl-CoA mutase, two enzymes implicated in key pathways for cell proliferation: methylation, purine synthesis, succinylation and ATP production. Ensuring these functions in cancer cells therefore requires important cob...
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| Format: | Article |
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MDPI AG
2022-05-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/10/2058 |
| _version_ | 1797497239977852928 |
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| author | Valentin Lacombe Guy Lenaers Geoffrey Urbanski |
| author_facet | Valentin Lacombe Guy Lenaers Geoffrey Urbanski |
| author_sort | Valentin Lacombe |
| collection | DOAJ |
| description | Cobalamin or vitamin B12 (B12) is a cofactor for methionine synthase and methylmalonyl-CoA mutase, two enzymes implicated in key pathways for cell proliferation: methylation, purine synthesis, succinylation and ATP production. Ensuring these functions in cancer cells therefore requires important cobalamin needs and its uptake through the transcobalamin II receptor (TCII-R). Thus, both the TCII-R and the cobalamin-dependent metabolic pathways constitute promising therapeutic targets to inhibit cancer development. However, the link between cobalamin and solid cancers is not limited to cellular metabolism, as it also involves the circulating transcobalamins I and II (TCI or haptocorrin and TCII) carrier proteins, encoded by <i>TCN1</i> and <i>TCN2</i>, respectively. In this respect, elevations of B12, TCI and TCII concentrations in plasma are associated with cancer onset and relapse, and with the presence of metastases and worse prognosis. In addition, <i>TCN1</i> and <i>TCN2</i> overexpressions are associated with chemoresistance and a proliferative phenotype, respectively. Here we review the involvement of cobalamin and transcobalamins in cancer diagnosis and prognosis, and as potential therapeutic targets. We further detail the relationship between cobalamin-dependent metabolic pathways in cancer cells and the transcobalamins’ abundancies in plasma and tumors, to ultimately hypothesize screening and therapeutic strategies linking these aspects. |
| first_indexed | 2024-03-10T03:14:40Z |
| format | Article |
| id | doaj.art-afe7ad6db89042a28f26f6766c3b0ca3 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T03:14:40Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-afe7ad6db89042a28f26f6766c3b0ca32023-11-23T12:29:22ZengMDPI AGNutrients2072-66432022-05-011410205810.3390/nu14102058Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid CancersValentin Lacombe0Guy Lenaers1Geoffrey Urbanski2MitoLab Team, MitoVasc Institut, CNRS UMR6015, INSERM U1083, Angers University, 49000 Angers, FranceMitoLab Team, MitoVasc Institut, CNRS UMR6015, INSERM U1083, Angers University, 49000 Angers, FranceMitoLab Team, MitoVasc Institut, CNRS UMR6015, INSERM U1083, Angers University, 49000 Angers, FranceCobalamin or vitamin B12 (B12) is a cofactor for methionine synthase and methylmalonyl-CoA mutase, two enzymes implicated in key pathways for cell proliferation: methylation, purine synthesis, succinylation and ATP production. Ensuring these functions in cancer cells therefore requires important cobalamin needs and its uptake through the transcobalamin II receptor (TCII-R). Thus, both the TCII-R and the cobalamin-dependent metabolic pathways constitute promising therapeutic targets to inhibit cancer development. However, the link between cobalamin and solid cancers is not limited to cellular metabolism, as it also involves the circulating transcobalamins I and II (TCI or haptocorrin and TCII) carrier proteins, encoded by <i>TCN1</i> and <i>TCN2</i>, respectively. In this respect, elevations of B12, TCI and TCII concentrations in plasma are associated with cancer onset and relapse, and with the presence of metastases and worse prognosis. In addition, <i>TCN1</i> and <i>TCN2</i> overexpressions are associated with chemoresistance and a proliferative phenotype, respectively. Here we review the involvement of cobalamin and transcobalamins in cancer diagnosis and prognosis, and as potential therapeutic targets. We further detail the relationship between cobalamin-dependent metabolic pathways in cancer cells and the transcobalamins’ abundancies in plasma and tumors, to ultimately hypothesize screening and therapeutic strategies linking these aspects.https://www.mdpi.com/2072-6643/14/10/2058neoplasmsvitamin B12transcobalaminsmethioninemetabolismmethylation |
| spellingShingle | Valentin Lacombe Guy Lenaers Geoffrey Urbanski Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers Nutrients neoplasms vitamin B12 transcobalamins methionine metabolism methylation |
| title | Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers |
| title_full | Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers |
| title_fullStr | Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers |
| title_full_unstemmed | Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers |
| title_short | Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers |
| title_sort | diagnostic and therapeutic perspectives associated to cobalamin dependent metabolism and transcobalamins synthesis in solid cancers |
| topic | neoplasms vitamin B12 transcobalamins methionine metabolism methylation |
| url | https://www.mdpi.com/2072-6643/14/10/2058 |
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