Nature Communications (Feb 2024)
Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses
- Seong Eun Lee,
- Seongyeol Park,
- Shinae Yi,
- Na Rae Choi,
- Mi Ae Lim,
- Jae Won Chang,
- Ho-Ryun Won,
- Je Ryong Kim,
- Hye Mi Ko,
- Eun-Jae Chung,
- Young Joo Park,
- Sun Wook Cho,
- Hyeong Won Yu,
- June Young Choi,
- Min-Kyung Yeo,
- Boram Yi,
- Kijong Yi,
- Joonoh Lim,
- Jun-Young Koh,
- Min Jeong Lee,
- Jun Young Heo,
- Sang Jun Yoon,
- Sung Won Kwon,
- Jong-Lyul Park,
- In Sun Chu,
- Jin Man Kim,
- Seon-Young Kim,
- Yujuan Shan,
- Lihua Liu,
- Sung-A Hong,
- Dong Wook Choi,
- Junyoung O. Park,
- Young Seok Ju,
- Minho Shong,
- Seon-Kyu Kim,
- Bon Seok Koo,
- Yea Eun Kang
Affiliations
- Seong Eun Lee
- Research Center for Endocrine and Metabolic Disease, College of Medicine, Chungnam National University
- Seongyeol Park
- GENOME INSIGHT TECHNOLOGY Inc
- Shinae Yi
- Research Center for Endocrine and Metabolic Disease, College of Medicine, Chungnam National University
- Na Rae Choi
- Research Center for Endocrine and Metabolic Disease, College of Medicine, Chungnam National University
- Mi Ae Lim
- Research Institute for Medical Sciences, College of Medicine, Chungnam National University
- Jae Won Chang
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University
- Ho-Ryun Won
- Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University
- Je Ryong Kim
- Department of Surgery, College of Medicine, Chungnam National University
- Hye Mi Ko
- Department of Surgery, College of Medicine, Chungnam National University
- Eun-Jae Chung
- Department of Otolaryngology-Head and Neck Surgery, Seoul National University College of Medicine
- Young Joo Park
- Department of Internal Medicine, Seoul National University College of Medicine
- Sun Wook Cho
- Department of Internal Medicine, Seoul National University College of Medicine
- Hyeong Won Yu
- Department of Surgery, Seoul National University Bundang Hospital
- June Young Choi
- Department of Surgery, Seoul National University Bundang Hospital
- Min-Kyung Yeo
- Department of Pathology, College of Medicine, Chungnam National University
- Boram Yi
- GENOME INSIGHT TECHNOLOGY Inc
- Kijong Yi
- GENOME INSIGHT TECHNOLOGY Inc
- Joonoh Lim
- GENOME INSIGHT TECHNOLOGY Inc
- Jun-Young Koh
- GENOME INSIGHT TECHNOLOGY Inc
- Min Jeong Lee
- Department of Biochemistry, College of Medicine, Chungnam National University
- Jun Young Heo
- Department of Biochemistry, College of Medicine, Chungnam National University
- Sang Jun Yoon
- College of Pharmacy, Seoul National University
- Sung Won Kwon
- College of Pharmacy, Seoul National University
- Jong-Lyul Park
- Korea Research Institute of Bioscience and Biotechnology
- In Sun Chu
- Korea Research Institute of Bioscience and Biotechnology
- Jin Man Kim
- Department of Pathology, College of Medicine, Chungnam National University
- Seon-Young Kim
- Korea Research Institute of Bioscience and Biotechnology
- Yujuan Shan
- Department of Nutrition, School of Public Health and Management, Wenzhou Medical University
- Lihua Liu
- Department of Nutrition, School of Public Health and Management, Wenzhou Medical University
- Sung-A Hong
- Department of Biochemistry, Chungnam National University
- Dong Wook Choi
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University
- Junyoung O. Park
- Department of Chemical and Biomolecular Engineering, University of California, Los Angeles
- Young Seok Ju
- GENOME INSIGHT TECHNOLOGY Inc
- Minho Shong
- Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology
- Seon-Kyu Kim
- Korea Research Institute of Bioscience and Biotechnology
- Bon Seok Koo
- Research Institute for Medical Sciences, College of Medicine, Chungnam National University
- Yea Eun Kang
- Research Center for Endocrine and Metabolic Disease, College of Medicine, Chungnam National University
- DOI
- https://doi.org/10.1038/s41467-024-45366-0
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 17
Abstract
Abstract The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.
