A distinct pattern of one-carbon metabolism in invasive breast cancer

Volume 11, Issue 18 of @Oncotarget reported that activation of one-carbon metabolism in tumor cells can sustain oncogenesis while contributing to epigenetic changes and metabolic adaptation during tumor progression.

The authors assessed whether increased one-carbon metabolism activity is a metabolic feature of invasive ductal carcinoma.

Their targeted metabolomics analysis showed distinct metabolomics profiles between IDC and adjacent tissue, where IDC displayed a comparative enrichment of metabolites involved in one-carbon metabolism and a predicted increase in the activity of pathways that receive and donate carbon units.

Dr. Jéssica Reis Santos from The Gastroenterology Department at The University of São Paulo School of Medicine (FMUSP), São Paulo, Brazil, said: "Breast cancer is the most common malignancy in women and the leading cause of their cancer-related deaths, with an estimated 23% prevalence and 14% mortality rate worldwide."

"Breast cancer is the most common malignancy in women and the leading cause of their cancer-related deaths, with an estimated 23% prevalence and 14% mortality rate worldwide."

- Dr. Jéssica Reis Santos, The Gastroenterology Department at The University of São Paulo School of Medicine (FMUSP)

Screening for metabolic signatures of tumor cells by omics platforms has substantially contributed to a better understanding of cancer metabolism and behavior.

One-carbon metabolism is activated in some cancers and can provide the building blocks and reducing the power required to maintain high cell proliferation rates, a key feature of oncogenesis.

Mutations in TP53 and MYC, which are common in breast tumors, seem to increase one-carbon metabolism activity.

Figure 1: Tissue metabolomics multivariate analysis. BC-T: IDC; BC-S: non-tumor adjacent breast tissue. (A) Principal component analysis (PCA) showing the natural separation between breast tumor and non-tumor adjacent breast tissues. (B) Partial least square discriminant analysis (PLS-DA) showing robust separation among the groups (BC-T vs BC-S). Each point in the plot corresponds to a tissue sample.

Aiming to contribute to the understanding of breast carcinogenesis and the identification of potential treatment targets, here we assessed whether the increased activity of one-carbon metabolism is a metabolic feature of breast cancers and whether it may represent a potential target for its treatment and prevention.

The Santos Research Team concluded in their Oncotarget Research Article, "taken together, our results support the ancillary role of several metabolic pathways in breast cancer progression, where one-carbon metabolism activation seems to be pivotal. The extent to which these metabolic pathways represent real vulnerabilities remains to be determined. Considering whether this pathway is sensitive to the availability of nutrients, dietary management should be explored, as well as the effectiveness (from a metabolomic perspective) of antimetabolic drugs, including metformin, 5-FLU, methotrexate, pemetrexed and other agents targeting one-carbon metabolism that have demonstrated clinical benefits."

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DOI - https://doi.org/10.18632/oncotarget.27575

Full text - https://www.oncotarget.com/article/27575/text/

Correspondence to - Jéssica Reis Santos - jeeh.reis@hotmail.com

Keywords - invasive ductal carcinoma, targeted metabolomics, untargeted metabolomics, tumor metabolism, one-carbon metabolism

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