[en] 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.
Disciplines :
Oncologie
Auteur, co-auteur :
MEISER, Johannes ; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Schuster, Anne; Department of Oncology, NorLux Neuro-Oncology Laboratory, Luxembourg Institute of Health, L-1526, Luxembourg, Luxembourg.
Pietzke, Matthias; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Vande Voorde, Johan; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Athineos, Dimitris ; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Oizel, Kristell; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Dhayade, Sandeep; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Morton, Jennifer P; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK. ; Institute for Cancer Sciences, University of Glasgow, G61 1BD, Glasgow, UK.
Dornier, Emmanuel ; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Sumpton, David; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Mackay, Gillian M; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Blyth, Karen ; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Patel, Ketan J; MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK. ; Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 2QQ, UK.
NICLOU, Simone P. ; Department of Oncology, NorLux Neuro-Oncology Laboratory, Luxembourg Institute of Health, L-1526, Luxembourg, Luxembourg. ; Department of Biomedicine, Kristian Gerhard Jebsen Brain Tumour Research Center, University of Bergen, Bergen, N-5009, Norway.
Vazquez, Alexei ; Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK. a.vazquez@beatson.gla.ac.uk. ; Institute for Cancer Sciences, University of Glasgow, G61 1BD, Glasgow, UK. a.vazquez@beatson.gla.ac.uk.
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