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Metabolic Alterations in Preneoplastic Development Revealed by Untargeted Metabolomic Analysis
Henna Myllymäki1, Jeanette Astorga Johansson1, Estefania Grados Porro1
1Centre for Inflammation Research, Queen's Medical Research Institute, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh, United Kingdom.
Frontiers in Cell and Developmental Biology
|August 20, 2021
Summary
This study reveals key metabolic shifts during pre-neoplastic cell development, identifying altered pathways crucial for early tumor growth. These findings offer new insights into cancer initiation and progression.
Area of Science:
- Oncology
- Metabolomics
- Zebrafish models
Background:
- Metabolic rewiring is vital for cancer development, but early changes during pre-neoplastic cell (PNC) progression are poorly understood.
- Existing research primarily focuses on established tumors and cancer cell lines, leaving a gap in knowledge regarding initial metabolic alterations.
Purpose of the Study:
- To investigate metabolic changes during oncogene-induced pre-neoplastic cell development.
- To identify key metabolic pathways involved in the transition from pre-neoplastic lesions to tumors.
Main Methods:
- Utilized untargeted metabolomics analysis in a transgenic inducible zebrafish larval skin model.
- Compared metabolic profiles of HRASG12V-induced pre-neoplastic cells with normal sibling controls.
Main Results:
- Identified six significantly altered metabolic pathways during PNC development in zebrafish skin.
- Observed alterations in pyrimidine, purine, and amino acid metabolism, supporting rapid cell proliferation.
- Detected potential alterations in RNA post-transcriptional modification during PNC development.
Conclusions:
- The study provides a workflow for identifying metabolic alterations at the onset of oncogenic mutations.
- Findings highlight the role of specific metabolic pathways and RNA modifications in early tumor development.
- This approach can be integrated with transcriptomics or proteomics for a comprehensive understanding of early tumorigenesis.
