Constructing interactive networks of functional genes and metabolites to uncover the cellular events related to colorectal cancer cell migration induced by arsenite

Abstract

Tumor cell migration induced by arsenite (iAsIII) is closely associated with cancer progression. However, transcriptomic and metabolic traits of migrative human cells exposed to iAsIII remain to be well characterized. Here, the combination of transcriptomics and metabolomics approaches were employed to construct interactive networks of functional genes and metabolites in human colorectal cancer (DLD-1) cells exposed to iAsIII. The number of DLD-1 cells passing through the Transwell membrane was at least 6 times greater in the iAsIII-treated groups than in controls. Following iAsIII treatment, the expression of ZEB1 and SLUG protein was significantly upregulated while the expression of CRB2 was downregulated (p < 0.05), indicating the onset of epithelial to mesenchymal transition (EMT). Meanwhile, integrin- and collagen-mediated biological adhesion were enhanced by SLUG under iAsIII treatment. The expression of matrix metallopeptidase (MMP) genes was fostered by iAsIII, which have the functions to degrade extracellular matrix. Glutamine metabolism could be considerably interfered by iAsIII, and in turn glutamine supplementation could effectively enhance DLD-1 cell movement. Overall, our results suggested that DLD-1 cell migration could be promoted by iAsIII via a series of cellular events, including EMT activation, altered cell adhesion, MMP-dependent matrix degradation, accompanying with a metabolic focus on glutamine.

Keywords

• Cell migration
• Arsenite
• Epithelial to mesenchymal transition
• Extracellular matrix
• Glutamine