摘要
Mutations leading to constitutive activation of the Wnt pathway and its target genes are frequently observed in cancer. The Wnt pathway promotes cell proliferation and increasing evidence supports its role also in cancer cell metabolism. This study aims to elucidate the role of the Wnt/β-catenin target gene CCND1 in these processes in colorectal cancer. We analyzed whether knock-down of CCND1 affects cell cycle progression and energy metabolism in a colorectal cancer cell line. Down-regulation of CCND1 led to retardation of the cell cycle. The proportion of cells in the G0 phase increased, while the amount of cells in the S- and G2/M phase decreased. Interestingly, knock-down of CCND1 changed the perinuclear localization of mitochondria into a homogeneous distribution within the cytosol. In addition CCND1 knock-down led to an increase of the intracellular ATP level indicating that cyclin D1 reduced mitochondrial activity. Our findings suggest that in addition to its role in cell cycle regulation, the Wnt target gene CCND1 regulates mitochondrial localization and inhibits mitochondrial activity in colorectal cancer cells.
Mutations leading to constitutive activation of the Wnt pathway and its target genes are frequently observed in cancer. The Wnt pathway promotes cell proliferation and increasing evidence supports its role also in cancer cell metabolism. This study aims to elucidate the role of the Wnt/β-catenin target gene CCND1 in these processes in colorectal cancer. We analyzed whether knock-down of CCND1 affects cell cycle progression and energy metabolism in a colorectal cancer cell line. Down-regulation of CCND1 led to retardation of the cell cycle. The proportion of cells in the G0 phase increased, while the amount of cells in the S- and G2/M phase decreased. Interestingly, knock-down of CCND1 changed the perinuclear localization of mitochondria into a homogeneous distribution within the cytosol. In addition CCND1 knock-down led to an increase of the intracellular ATP level indicating that cyclin D1 reduced mitochondrial activity. Our findings suggest that in addition to its role in cell cycle regulation, the Wnt target gene CCND1 regulates mitochondrial localization and inhibits mitochondrial activity in colorectal cancer cells.
作者
Annica Vlad-Fiegen
Natalie Veronika Freytag
Susanne Dorn
Oliver Müller
Sonja Eberth
Annica Vlad-Fiegen;Natalie Veronika Freytag;Susanne Dorn;Oliver Müller;Sonja Eberth(DLR Project Management Agency, German Aerospace Center, Bonn, Germany;Molecular Cancer Research, Leibniz Institute DMSZ, Braunschweig, Germany;Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany;University of Applied Sciences Kaiserslautern, Zweibrücken, Germany)
