Increased formate overflow is a hallmark of oxidative cancer
| العنوان: | Increased formate overflow is a hallmark of oxidative cancer |
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| المؤلفون: | Matthias Pietzke, Jennifer P. Morton, Simone P. Niclou, Anne Schuster, David Sumpton, Ketan J. Patel, Niek Wit, Guillermo Burgos-Barragan, Johan Vande Voorde, Johannes Meiser, Kristell Oizel, Dimitris Athineos, Gillian M. Mackay, Emmanuel Dornier, Karen Blyth, Alexei Vazquez, Sandeep Dhayade |
| المصدر: | Nature Communications, Vol 9, Iss 1, Pp 1-12 (2018) Nature Communications |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adenoma, Male, 0301 basic medicine, Antimetabolites, Antineoplastic, Formates, Science, education, General Physics and Astronomy, Oxidative phosphorylation, Article, General Biochemistry, Genetics and Molecular Biology, Serine, Mice, 03 medical and health sciences, chemistry.chemical_compound, Mammary Glands, Animal, Mammary tumor virus, Cell Line, Tumor, Intestinal Neoplasms, Tumor Microenvironment, Animals, Formate, Intestinal Mucosa, lcsh:Science, Glycine Hydroxymethyltransferase, Tumor microenvironment, Multidisciplinary, Chemistry, Catabolism, Mammary Neoplasms, Experimental, General Chemistry, Mitochondria, Gene Expression Regulation, Neoplastic, Intestines, Isoenzymes, Mice, Inbred C57BL, Methotrexate, 030104 developmental biology, Mammary Tumor Virus, Mouse, Biochemistry, Cell culture, Cancer cell, Female, lcsh:Q, Oxidation-Reduction |
| الوصف: | Formate overflow coupled to mitochondrial oxidative metabolism\ has been observed in cancer cell lines, but whether that takes place in the tumor microenvironment is not known. Here we report the observation of serine catabolism to formate in normal murine tissues, with a relative rate correlating with serine levels and the tissue oxidative state. Yet, serine catabolism to formate is increased in the transformed tissue of in vivo models of intestinal adenomas and mammary carcinomas. The increased serine catabolism to formate is associated with increased serum formate levels. Finally, we show that inhibition of formate production by genetic interference reduces cancer cell invasion and this phenotype can be rescued by exogenous formate. We conclude that increased formate overflow is a hallmark of oxidative cancers and that high formate levels promote invasion via a yet unknown mechanism. Serine catabolism to formate supplies one-carbon units for biosynthesis. Here the authors show that formate production in murine cancers with high oxidative metabolism exceeds the biosynthetic demand and that high formate levels promotes invasion of cancer cells. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9d8b508ef3e7c99a457bcfa089bdda54Test https://eprints.gla.ac.uk/161017/1/161017.pdfTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9d8b508ef3e7c99a457bcfa089bdda54 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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