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Background: Colon cancer is the second leading cancer worldwide. Recurrent disease and chemotherapeutic drug resistance are very common in the advanced stage of colon cancer. ATP-citrate lyase (ACLY), the first-step rate-controlling enzyme in lipid synthesis, is elevated in colon cancer. However, it remains unclear about the exact role of ACLY in the development of colon cancer metastasis. Methods: To evaluate the role of ACLY in colon cancer metastasis, we performed cell migration and invasion assays in two ACLY-deficient colon cancer cell lines. Colon cancer mouse model is used to examine ACLY's effects on colon metastasis potentials in vivo. We analyzed the correlation between ACLY and CTNNB1 protein in 78 colon cancer patients by Pearson correlation. To finally explore the relationship of ACLY and CTNNB1, we used western blots, migration and invasion assays to confirm that ACLY may regulate metastasis by CTNNB1. Results: Our data showed that the abilities of cell migration and invasion were attenuated in ACLY-deficient HCT116 and RKO cell lines. Furthermore, we describe the mechanism of ACLY in promoting colon cancer metastasis in vitro and in vivo. ACLY could stabilize CTNNB1 (beta-catenin 1) protein by interacting, and the complex might promote CTNNB1 translocation through cytoplasm to nucleus, subsequently promote the CTNNB1 transcriptional activity and migration and invasion abilities of colon cancer cells. Immunohistochemical analysis of 78 colon cancer patients showed that the high expression levels of ACLY and CTNNB1 protein was positively correlated with metastasis of colon cancer. Conclusions: These results shed new light on the molecular mechanism underlying colon cancer metastasis, which might help in improving therapeutic efficacy. [ABSTRACT FROM AUTHOR]

TIGAR is a p53 target gene that is known to protect cells from ROS-induced apoptosis by promoting the pentose phosphate pathway. The role of TIGAR in tumor cell invasion and metastasis remains elusive. Here we found that downregulation of TIGAR reduced the invasion and metastasis of NSCLC cells in vitro and in vivo. Immunohistochemical analysis of 72 NSCLC patients showed that TIGAR and Met protein expression was positively correlated with late stages of lung cancer. Besides, patients with high co-expression of TIGAR and Met presented a significantly worse survival. In addition, we found that Met signaling pathway is involved in TIGAR-induced invasion and metastasis. Our study indicates that TIGAR/Met pathway may be a novel target for NSCLC therapy. It is necessary to evaluate the expression of TIGAR before Met inhibitors are used for NSCLC treatment. [ABSTRACT FROM AUTHOR]