Gene Expression Profiling And Metabolomic Studies On Metabolic Pathways Altered In Colorectal Cancer Tissues

In line with the idea that abnormal metabolism is a hallmark of cancer,malignant cancer cells often exhibit abnormal metabolic pathways in direct relationship with increased cell survival,proliferation and capacity of invasion as well as metastasis.Altered levels of diverse intracellular metabolites,which also constitute in vivo tumor metabolic microenvironments,are largely attributed to altered expression of relevant genes that encode corresponding metabolic enzymes;these changes can be detected by gene expression profiling and metabolomic studies.Here,we use the colorectal cancer(CRC)tissue samples as a model system,in an effort to build a map of altered metabolic pathways during cancer development.We classified the CRC tissues and adjacent specimens into several stages from normal to metastasis,and used the aforementioned methodologies to study the changed metabolic pathways during CRC malignancy.Furthermore,we verified the impact of abnormal metabolic pathways in nucleoside/nucleotide metabolism(inosine and related metabolites)in CRC tumor cells focusing,especially,on the behavior of IMPDH2(inosine 5’-monophosphate dehydrogenase 2)in comparison with that in adjacent normal tissues.Our results suggest that altered expression of metabolic enzymes and altered levels of certain metabolites in a variety of metabolic pathways in CRC tissues represent an important indicator for growth advantage unique to malignant cancer cells.These findings give us thinkling that efficient tumor intervention strategies(or the next generation anticancer drugs)may derive from chemicals that target a number of important metabolic enzymes.