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Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.
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.
Afiliación
  • Lee SE; Research Center for Endocrine and Metabolic Disease, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Park S; Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Yi S; GENOME INSIGHT TECHNOLOGY Inc, Daejeon, Republic of Korea.
  • Choi NR; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Lim MA; Research Center for Endocrine and Metabolic Disease, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Chang JW; Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Won HR; Research Center for Endocrine and Metabolic Disease, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Kim JR; Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Ko HM; Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Chung EJ; Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Park YJ; Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Cho SW; Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Yu HW; Department of Surgery, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Choi JY; Department of Surgery, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Yeo MK; Department of Otolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Yi B; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Yi K; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Lim J; Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
  • Koh JY; Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.
  • Lee MJ; Department of Pathology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Heo JY; GENOME INSIGHT TECHNOLOGY Inc, Daejeon, Republic of Korea.
  • Yoon SJ; GENOME INSIGHT TECHNOLOGY Inc, Daejeon, Republic of Korea.
  • Kwon SW; GENOME INSIGHT TECHNOLOGY Inc, Daejeon, Republic of Korea.
  • Park JL; GENOME INSIGHT TECHNOLOGY Inc, Daejeon, Republic of Korea.
  • Chu IS; Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Kim JM; Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Kim SY; College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
  • Shan Y; College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
  • Liu L; Korea Research Institute of Bioscience and Biotechnology, Deajeon, Republic of Korea.
  • Hong SA; Korea Research Institute of Bioscience and Biotechnology, Deajeon, Republic of Korea.
  • Choi DW; Department of Bioscience, University of Science and Technology (UST), Deajeon, Republic of Korea.
  • Park JO; Department of Pathology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
  • Ju YS; Korea Research Institute of Bioscience and Biotechnology, Deajeon, Republic of Korea.
  • Shong M; Department of Bioscience, University of Science and Technology (UST), Deajeon, Republic of Korea.
  • Kim SK; Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
  • Koo BS; Department of Nutrition, School of Public Health and Management, Wenzhou Medical University, Wenzhou, 325035, China.
  • Kang YE; Department of Nutrition, School of Public Health and Management, Wenzhou Medical University, Wenzhou, 325035, China.
Nat Commun ; 15(1): 1163, 2024 Feb 08.
Article en En | MEDLINE | ID: mdl-38331894
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Tiroides / Multiómica Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Tiroides / Multiómica Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article