2. Academic Validation
  3. Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses

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

  • Nat Commun. 2024 Feb 8;15(1):1163. doi: 10.1038/s41467-024-45366-0.
Seong Eun Lee # 1 2,  Seongyeol Park # 3 4,  Shinae Yi 1 2,  Na Rae Choi 1 2,  Mi Ae Lim 2 5,  Jae Won Chang 5,  Ho-Ryun Won 5,  Je Ryong Kim 6,  Hye Mi Ko 6,  Eun-Jae Chung 7,  Young Joo Park 8,  Sun Wook Cho 8,  Hyeong Won Yu 9,  June Young Choi 9,  Min-Kyung Yeo 10,  Boram Yi 3,  Kijong Yi 3,  Joonoh Lim 3,  Jun-Young Koh 3,  Min Jeong Lee 11,  Jun Young Heo 11,  Sang Jun Yoon 12,  Sung Won Kwon 12,  Jong-Lyul Park 13,  In Sun Chu 13 14,  Jin Man Kim 10,  Seon-Young Kim 13 14 15,  Yujuan Shan 16,  Lihua Liu 16,  Sung-A Hong 17,  Dong Wook Choi 18,  Junyoung O Park 19,  Young Seok Ju 3 20,  Minho Shong 20,  Seon-Kyu Kim 21,  Bon Seok Koo 22 23,  Yea Eun Kang 24 25 26
Affiliations

Affiliations

  • 1 Research Center for Endocrine and Metabolic Disease, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • 2 Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • 3 GENOME INSIGHT TECHNOLOGY Inc, Daejeon, Republic of Korea.
  • 4 Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • 5 Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • 6 Department of Surgery, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • 7 Department of Otolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 8 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 9 Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
  • 10 Department of Pathology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • 11 Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • 12 College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
  • 13 Korea Research Institute of Bioscience and Biotechnology, Deajeon, Republic of Korea.
  • 14 Department of Bioscience, University of Science and Technology (UST), Deajeon, Republic of Korea.
  • 15 Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
  • 16 Department of Nutrition, School of Public Health and Management, Wenzhou Medical University, Wenzhou, 325035, China.
  • 17 Department of Biochemistry, Chungnam National University, Daejeon, Republic of Korea.
  • 18 Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
  • 19 Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, USA.
  • 20 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
  • 21 Korea Research Institute of Bioscience and Biotechnology, Deajeon, Republic of Korea. [email protected].
  • 22 Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. [email protected].
  • 23 Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. [email protected].
  • 24 Research Center for Endocrine and Metabolic Disease, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. [email protected].
  • 25 Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. [email protected].
  • 26 Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Republic of Korea. [email protected].
  • # Contributed equally.
PMID: 38331894 DOI: 10.1038/s41467-024-45366-0
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.

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