CtBP1 associates metabolic syndrome and breast carcinogenesis targeting multiple miRNAs.

DE LUCA P; DALTON N; SCALISE G; MOIOLA CP; PORRETTI J; MASSILLO CL; KORDON E; GARDNER K; ZALAZAR F; FLUMIAN C; TODARO L; VAZQUEZ ES; MEISS R; DE SIERVI A

Oncotarget

Impact Journals

Año: 2016 vol. 7 p. 18798 - 18811

Metabolic syndrome (MeS) has been identified as a risk factor for breast cancer.C-terminal binding protein 1 (CtBP1) is a co-repressor of tumor suppressor genesthat is activated by low NAD+/NADH ratio. High fat diet (HFD) increases intracellularNADH. We investigated the effect of CtBP1 hyperactivation by HFD intake on mousebreast carcinogenesis. We generated a MeS-like disease in female mice by chronicallyfeeding animals with HFD. MeS increased postnatal mammary gland developmentand generated prominent duct patterns with markedly increased CtBP1 and Cyclin D1expression. CtBP1 induced breast cancer cells proliferation. Serum from animals withMeS enriched the stem-like/progenitor cell population from breast cancer cells. CtBP1increased breast tumor growth in MeS mice modulating multiple genes and miRNAexpression implicated in cell proliferation, progenitor cells phenotype, epithelialto mesenchymal transition, mammary development and cell communication in thexenografts. These results define a novel function for CtBP1 in breast carcinogenesis