1. Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses
- Author
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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, and Yea Eun Kang
- Subjects
Science - 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.
- Published
- 2024
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