Details

Autor(en) / Beteiligte

• 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

Titel

Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses

Ist Teil von

• Nature communications, 2024-02, Vol.15 (1), p.1163-1163, Article 1163

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2024

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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. Different types of metabolic rewiring are reported to drive cancer development and as a potential therapeutic target. Here, the authors perform multi-omics analyses in a cohort of human normal and malignant thyroid samples and show association of mitochondrial one-carbon metabolism with undifferentiated thyroid cancer.