Article
Age-associated mitochondrial DNA mutations cause metabolic remodelling that contributes to accelerated intestinal tumorigenesis.
Nature cancer - 1 Oct 2020
Smith Anna Lm, Whitehall Julia C, Bradshaw Carla, Gay David, Robertson Fiona, Blain Alasdair P, Hudson Gavin, Pyle Angela, Houghton David, Hunt Matthew, Sampson James N, Stamp Craig, Mallett Grace, Amarnath Shoba, Leslie Jack, Oakley Fiona, Wilson Laura, Baker Angela, Russell Oliver M, Johnson Riem, Richardson Claire A, Gupta Bhavana, McCallum Iain, McDonald Stuart Ac, Kelly Seamus, Mathers John C, Heer Rakesh, Taylor Robert W, Perkins Neil D, Turnbull Doug M, Sansom Owen J, Greaves Laura C
Abstract excerpt
Oxidative phosphorylation (OXPHOS) defects caused by somatic mitochondrial DNA (mtDNA) mutations increase with age in human colorectal epithelium and are prevalent in colorectal tumours, but whether they actively contribute to tumorigenesis remains unknown. Here we demonstrate that mtDNA mutations causing OXPHOS defects are enriched during the human adenoma/carcinoma sequence, suggesting they may confer a...
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