Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Metabolome-Wide Reprogramming Modulated by Wnt/β-Catenin Signaling Pathway

  • Soo Jin Park (Department of Agricultural Biotechnology, Seoul National University) ;
  • Joo-Hyun Kim (Department of Bio and Fermentation Convergence Technology, Kookmin University) ;
  • Sangtaek Oh (Department of Bio and Fermentation Convergence Technology, Kookmin University) ;
  • Do Yup Lee (Department of Agricultural Biotechnology, Seoul National University)
  • Received : 2022.11.07
  • Accepted : 2022.11.14
  • Published : 2023.01.28
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Abstract

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 (β-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.

Keywords

Acknowledgement

This research was funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea [grant numbers HU20C0187] and was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through High Value-added Food Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA; 321036-05-1-HD020). This work was also supported bythe "Cooperative Research Program for Agriculture Science and Technology Development (Project No. PJ015865012021)" Rural Development Administration, Republic of Korea.

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