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Lee, Seong Eun; Park, Seongyeol; Yi, Shinae; Choi, Na Rae; Lim, Mi Ae; Chang, Jae Won; Won, Ho-Ryun; Kim, Je Ryong; Ko, Hye Mi; Chung, Eun-Jae; Park, Young Joo; Cho, Sun Wook; Yu, Hyeong Won; Choi, June Young; Yeo, Min-Kyung; Yi, Boram; Yi, Kijong; Lim, Joonoh; Koh, Jun-Young; Lee, Min Jeong; Heo, Jun Young; Yoon, Sang Jun; Kwon, Sung Won; Park, Jong-Lyul; Chu, In Sun; Kim, Jin Man; Kim, Seon-Young; Shan, Yujuan; Liu, Lihua; Hong, Sung-A; Choi, Dong Wook; Park, Junyoung O; Ju, Young Seok; Shong, Minho; Kim, Seon-Kyu; Koo, Bon Seok; Kang, Yea Eun
Nature communications, 02/2024, Letnik: 15, Številka: 1Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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