Inherited cancer predisposition sensitizes colonic mucosa to address Western diet effects and putative cancer-predisposing changes on mouse proteome

Denis Đermadi Bebek, Satu Valo, Marjaana Pussila, Nima Reyhani, Laura Sarantaus, Maciej Lalowski, Marc Baumann, Minna Nyström

Human epidemiological evidence and previous studies on mice have shown that Western style diet (WD) may predispose gut mucosa to colorectal cancer (CRC). The mechanisms, which mediate the effects of diet on tumorigenesis are largely unknown. To address putative cancer predisposing events available for early detection, we quantitatively analyzed the proteome of histologically normal colon of a wild type (Mlh1+/+) and an Mlh1+/- mouse after a long term feeding experiment with WD and AIN-93G control diet. The Mlh1+/- mouse carries susceptibility to colon cancer analogous to a human CRC syndrome (Lynch syndrome). Remarkably, WD seemed to induce expression changes reflecting metabolic disturbances especially in the cancer predisposed colon, while similar changes were not significant in the wild type proteome. Overall, the detected changes constitute a complex interaction network of proteins involved in ATP synthesis coupled proton transport, oxidoreduction coenzyme and nicotinamide nucleotide metabolic processes, important in cell protection against ROS toxicity. Of these proteins, SELENBP1 and LGALS4 are underlined in neoplastic processes, which directly interact with MLH1, suggesting that sensitivity to WD is increased by an Mlh1 mutation. The significance of WD on CRC risk is highlighted by the fact that 5 out of 6 mice with neoplasias were fed with WD.

The Journal of Nutritional Biochemistry, 2014.