GSE167947
Mitochondrial matrix protein C14orf159 attenuates colorectal cancer metastasis through suppression of Wnt/ß-catenin signaling
Despite the progression in understanding the molecular events in colorectal tumorigenesis, the mechanisms underlying metastasis remain unclear. Recently, altered metabolism including mitochondrial function of cancer cells has emerged as an important factor which regulates metastatic capability of cancer. Here, we show that mitochondrial matrix protein C14orf159 attenuates colorectal cancer metastasis by suppressing Wnt/ß-catenin signaling. We demonstrated that C14orf159 maintained mitochondrial membrane potential of human colorectal cancer cells and was involved in amino acids and glutathione metabolism. In human colorectal cancer specimens, expression of C14orf159 was decreased in the tumor invasive fronts and metastatic lesions. C14orf159 attenuated the capability of migration, invasion and spheroid growth in colorectal cancer cells in vitro and colorectal tumor growth and metastasis in vivo. Mechanistically, C14orf159 reduced expression of the genes involved in colorectal cancer metastasis including WNT and MMP family partly by maintaining mitochondrial membrane potential. These findings provide a new link between mitochondrial membrane potential and Wnt/ß-catenin signaling, and uncover the novel function of the mitochondrial matrix protein C14orf159 as a suppressor in colorectal cancer metastasis. Overall design: To explore why C14orf159 decreases migration and invasion capability and spheroid growth in human colorectal cancer cells, we conducted RNA-seq analysis in C14orf159-KO and control HCT116 cells.