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Metabolites
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One Carbon Metabolism in Human Cancer
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One Carbon Metabolism in Human Cancer

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Cell Metabolism".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 4656

Special Issue Editor

Dr. Hanibal Bohnenberger

E-Mail Website
Guest Editor
Institute of Pathology, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, Germany
Interests: proteomics; lung cancer; cancer research; histopathology; molecular pathology; digital pathology; signaling pathways; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic remodeling in malignant neoplasias was first recognized nearly a century ago and is today one hallmark of human cancers that is used for diagnostic as well as therapeutic purposes. One Carbon Metabolism (1CM) includes the methionine and folate cycles and is crucial for nucleotide metabolism, genomic maintenance, and thus survival and proliferation of cancer cells. Therefore, chemotherapeutic drugs that affect the One Carbon Metabolism of tumor cells such as 5-FU, pemetrexed, and methotrexate are current first-line therapeutic strategies for numerous human cancers. Furthermore, several enzymes of this metabolic pathway have been shown to play a significant role in tumor initiation and progression in a variety of cancer entities, e.g., in pulmonary adenocarcinoma, colorectal cancer, acute myeloid leukemia, or Burkitt lymphoma. Especially MTHFD2, which catalyzes the transformation of methylene tetrahydrofolate, is strongly expressed in several different human cancers but is absent in most healthy adult tissues, making it a promising and highly relevant new drug target for better treatment of patients with cancer in future.

This Special Issue of Metabolites, “One Carbon Metabolism in Human Cancer”, will be dedicated to exploring both the functional role and the translational relevance of one carbon metabolism with the overall aim to improve the treatment and care of cancer patients. The topics that will be covered by this Special Issue include (though not exclusively) the usability of one 1CM activity or expression of its member as predictive of prognostic biomarkers, the suitability of 1CM members as new drug targets in cancer, the regulation of 1CM, e.g., by oncogenic mutations or epigenetic regulation, the consequences of 1CM activation and inhibition in cancer cells, the design of new and specific compounds to inhibit single members of the 1CM, and new techniques to investigate 1CM. Manuscripts dealing with other related issues are of course also highly desired.

Dr. Hanibal Bohnenberger
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • one carbon metabolism
  • cancer
  • MTHFD2
  • SHMT2
  • targeted therapy
  • biomarker
  • drug development

Published Papers (2 papers)

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Research

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15 pages, 2164 KiB  
Article
Regulation and Therapeutic Targeting of MTHFD2 and EZH2 in KRAS-Mutated Human Pulmonary Adenocarcinoma
by Yuchan Li, Omar Elakad, Sha Yao, Alexander von Hammerstein-Equord, Marc Hinterthaner, Bernhard C. Danner, Carmelo Ferrai, Philipp Ströbel, Stefan Küffer and Hanibal Bohnenberger
Metabolites 2022, 12(7), 652; https://doi.org/10.3390/metabo12070652 - 15 Jul 2022
Cited by 3 | Viewed by 2135
Abstract
Activating KRAS mutations occur in about 30% of pulmonary adenocarcinoma (AC) cases and the discovery of specific inhibitors of G12C-mutated KRAS has considerably improved the prognosis for a subgroup of about 14% of non-small cell lung cancer (NSCLC) patients. However, even in patients [...] Read more.
Activating KRAS mutations occur in about 30% of pulmonary adenocarcinoma (AC) cases and the discovery of specific inhibitors of G12C-mutated KRAS has considerably improved the prognosis for a subgroup of about 14% of non-small cell lung cancer (NSCLC) patients. However, even in patients with a KRAS G12C mutation, the overall response rate only reaches about 40% and mutations other than G12C still cannot be targeted. Despite the fact that one-carbon metabolism (1CM) and epigenetic regulation are known to be dysregulated by aberrant KRAS activity, we still lack evidence that co-treatment with drugs that regulate these factors might ameliorate response rates and patient prognosis. In this study, we show a direct dependency of Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) and Enhancer of Zeste Homolog 2 (EZH2) expression on mutationally activated KRAS and their prognostic relevance in KRAS-mutated AC. We show that aberrant KRAS activity generates a vulnerability of AC cancer cell lines to both MTHFD2 and EZH2 inhibitors. Importantly, co-inhibition of both factors was synergistically effective and comparable to KRASG12C inhibition alone, paving the way for their use in a therapeutic approach for NSCLC cancer patients. Full article
(This article belongs to the Special Issue One Carbon Metabolism in Human Cancer)
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Review

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18 pages, 2564 KiB  
Review
Targeted Proteomics for Monitoring One-Carbon Metabolism in Liver Diseases
by Laura Guerrero, Alberto Paradela and Fernando J. Corrales
Metabolites 2022, 12(9), 779; https://doi.org/10.3390/metabo12090779 - 24 Aug 2022
Cited by 5 | Viewed by 2111
Abstract
Liver diseases cause approximately 2 million deaths per year worldwide and had an increasing incidence during the last decade. Risk factors for liver diseases include alcohol consumption, obesity, diabetes, the intake of hepatotoxic substances like aflatoxin, viral infection, and genetic determinants. Liver cancer [...] Read more.
Liver diseases cause approximately 2 million deaths per year worldwide and had an increasing incidence during the last decade. Risk factors for liver diseases include alcohol consumption, obesity, diabetes, the intake of hepatotoxic substances like aflatoxin, viral infection, and genetic determinants. Liver cancer is the sixth most prevalent cancer and the third in mortality (second in males). The low survival rate (less than 20% in 5 years) is partially explained by the late diagnosis, which remarks the need for new early molecular biomarkers. One-carbon metabolism integrates folate and methionine cycles and participates in essential cell processes such as redox homeostasis maintenance and the regulation of methylation reactions through the production of intermediate metabolites such as cysteine and S-Adenosylmethionine. One-carbon metabolism has a tissue specific configuration, and in the liver, the participating enzymes are abundantly expressed—a requirement to maintain hepatocyte differentiation. Targeted proteomics studies have revealed significant differences in hepatocellular carcinoma and cirrhosis, suggesting that monitoring one-carbon metabolism enzymes can be useful for stratification of liver disease patients and to develop precision medicine strategies for their clinical management. Here, reprogramming of one-carbon metabolism in liver diseases is described and the role of mass spectrometry to follow-up these alterations is discussed. Full article
(This article belongs to the Special Issue One Carbon Metabolism in Human Cancer)
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