There is increasing evidence that glycolysis is involved in cancer progression. Aldolase is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Disruption of the aldolase genes also plays a role in the progression of multiple types of cancer. However, the underlying mechanism of the action of aldolases in colon cancer progression remains elusive. In this study, aldolase A expression was investigated and found to be upregulated along with human colon cancer progression and metastasis at both the mRNA and protein levels in human colon cancer tissues. In addition, silencing aldolase A suppressed colon cancer cell proliferation and invasion and inhibited the EMT phenotype. Aldolase A protein expression in colon cancer was related to tumor location, tumor clinical stage and survival. Kaplan-Meier analysis showed that high aldolase A protein expression was associated with an unfavorable outcome. Moreover, aldolase A affected the development of colon cancer not only by affecting the glucose metabolism but also by interacting with the HIF-1 and other EMT-related signaling pathways; silencing aldolase A resulted in the reduced activity of these signaling pathways. These results indicate that aldolase A has additional non-glycolytic functions in transcriptional EMT regulation and may therefore have potential as a therapeutic target or a biomarker for identifying patients at risk for poorer survival. (C) 2018 Elsevier Inc. All rights reserved.