한빛사논문
- 조회472
Yoo Hyung Kim1,*, Sang Jun Yoon2,*, Mina Kim2, Hwan Hee Kim1, Young Shin Song3,4 , Jin Woo Jung4, Dohyun Han4,5, Sun Wook Cho1, Sung Won Kwon2,#, Young Joo Park1,6,7,#
1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
2Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea
3Department of Internal Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea
4Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea
5Transdisciplinary Department of Medicine & Advanced Technology, Seoul National University Hospital, Seoul, Korea
6Department of Internal Medicine and Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine
7Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University
*These authors contributed equally to this work.
#These authors contributed equally as co-senior authors.
Correspondence to : Prof. Young Joo Park, Prof. Sung Won Kwon
Abstract
Purpose: Thyroid cancer (TC) metabolic characteristics vary depending on the molecular subtype determined by mutational status. We aimed to investigate the molecular subtype-specific metabolic characteristics of TCs.
Experimental design: An integrative multi-omics analysis was conducted, incorporating transcriptomics, metabolomics, and proteomics data obtained from human tissues representing distinct molecular characteristics of TCs; BRAF-like (papillary TC with BRAFV600E mutation; PTC-B), RAS-like (follicular TC with RAS mutation; FTC-R), and ATC-like (anaplastic TC with BRAFV600E or RAS mutation; ATC-B or ATC-R). To validate our findings, we employed tissue microarray of human TC tissues and performed in vitro analyses of cancer cell phenotypes and metabolomic assays after inducing genetic knockdown.
Results: Metabolic properties differed between differentiated TCs of PTC-B and FTC-R, but were similar in de-differentiated TCs of ATC-B/R, regardless of their mutational status. Tricarboxylic acid (TCA) intermediates and branched-chain amino acids (BCAA) were enriched with the activation of TCA cycle only in FTC-R, whereas one-carbon metabolism and pyrimidine metabolism increased in both PTC-B and FTC-R and to a great extent in ATC-B/R. However, the protein expression levels of the BCAA transporter (SLC7A5) and a key enzyme in one-carbon metabolism (SHMT2) increased in all TCs and were particularly high in ATC-B/R. Knockdown of SLC7A5 or SHMT2 inhibited the migration and proliferation of TC cell lines differently, depending on the mutational status.
Conclusions: These findings define the metabolic properties of each molecular subtype of TCs and identify metabolic vulnerabilities, providing a rationale for therapies targeting its altered metabolic pathways in advanced TC.
논문정보
- Research article
- 2023년 12월 (BRIC 등록일 2023-12-14)
- 국내 연구진
- 의약학 > 약학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
소속기관 논문보기
관련분야 논문보기
