Metabolome-Wide Reprogramming Modulated by Wnt/β-Catenin Signaling Pathway

A family of signal transduction pathways known as wingless type (Wnt) signaling pathways is essential to developmental processes like cell division and proliferation. Mutation in Wnt signaling results in a variety of diseases, including cancers of the breast, colon, and skin, metabolic disease, and neurodegenerative disease; thus, the Wnt signaling pathways have been attractive targets for disease treatment. However, the complicatedness and large involveness of the pathway often hampers pinpointing the specific targets of the metabolic process. In our current study, we investigated the differential metabolic regulation by the overexpression of the Wnt signaling pathway in a timely-resolved manner by applying high-throughput and un-targeted metabolite profiling. We have detected and annotated 321 metabolite peaks from a total of 36 human embryonic kidney (HEK) 293 cells using GC-TOF MS and LC-Orbitrap MS. The un-targeted metabolomic analysis identified the radical reprogramming of a range of central carbon/nitrogen metabolism pathways, including glycolysis, TCA cycle, and glutaminolysis, and fatty acid pathways. The investigation, combined with targeted mRNA profiles, elucidated an explicit understanding of activated fatty acid metabolism (beta-oxidation and biosynthesis). The findings proposed detailed mechanistic biochemical dynamics in response to Wnt-driven metabolic changes, which may help design precise therapeutic targets for Wnt-related diseases.

Automated summary

A family of signaling pathways called Wnt signaling pathways play a crucial role in developmental processes such as cell division and proliferation. Mutations in these pathways can lead to various diseases, including cancer, metabolic disorders, and neurodegenerative diseases. However, the complexity of these pathways makes it challenging to identify specific metabolic targets. In this study, the researchers used high-throughput and un-targeted metabolite profiling to investigate the metabolic regulation caused by the overexpression of the Wnt signaling pathway. They identified significant changes in central carbon/nitrogen metabolism pathways and fatty acid pathways. The findings provide a detailed understanding of the biochemical dynamics in response to Wnt-driven metabolic changes, which could help in the development of precise therapeutic targets for Wnt-related diseases.