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Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma. / Jin, Xing; Liu, Lei; Liu, Dan и др.

в: Cell Death and Differentiation, Том 31, № 5, 05.2024, стр. 558-573.

Результаты исследований: Научные публикации в периодических изданияхстатьяРецензирование

Harvard

Jin, X, Liu, L, Liu, D, Wu, J, Wang, C, Wang, S, Wang, F, Yu, G, Jin, X, Xue, YW, Jiang, D, Ni, Y, Yang, X, Wang, MS, Wang, ZW, Orlov, YL, Jia, W, Melino, G, Liu, JB & Chen, WL 2024, 'Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma', Cell Death and Differentiation, Том. 31, № 5, стр. 558-573. https://doi.org/10.1038/s41418-024-01285-7

APA

Jin, X., Liu, L., Liu, D., Wu, J., Wang, C., Wang, S., Wang, F., Yu, G., Jin, X., Xue, Y. W., Jiang, D., Ni, Y., Yang, X., Wang, M. S., Wang, Z. W., Orlov, Y. L., Jia, W., Melino, G., Liu, J. B., & Chen, W. L. (2024). Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma. Cell Death and Differentiation, 31(5), 558-573. https://doi.org/10.1038/s41418-024-01285-7

Vancouver

Jin X, Liu L, Liu D, Wu J, Wang C, Wang S и др. Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma. Cell Death and Differentiation. 2024 май;31(5):558-573. doi: 10.1038/s41418-024-01285-7

Author

Jin, Xing ; Liu, Lei ; Liu, Dan и др. / Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma. в: Cell Death and Differentiation. 2024 ; Том 31, № 5. стр. 558-573.

BibTeX

@article{c9b0d900efa24f5898fc05022067641b,
title = "Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma",
abstract = "Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.",
keywords = "Animals, Humans, Mice, Cell Line, Tumor, Cell Proliferation/drug effects, Esophageal Neoplasms/metabolism, Esophageal Squamous Cell Carcinoma/metabolism, Gene Expression Regulation, Neoplastic, Methionine/metabolism, Mice, Nude, Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism, Oncogenes",
author = "Xing Jin and Lei Liu and Dan Liu and Jia Wu and Congcong Wang and Siliang Wang and Fengying Wang and Guanzhen Yu and Xiaoxia Jin and Xue, {Yu Wen} and Dan Jiang and Yan Ni and Xi Yang and Wang, {Ming Song} and Wang, {Zhi Wei} and Orlov, {Yuriy L.} and Wei Jia and Gerry Melino and Liu, {Ji Bin} and Chen, {Wen Lian}",
note = "This work was supported by the National Key R&D Program of China (2023YFC3503200, 2023YFC3503201, 2022YFC3500200, 2022YFC3500202), National Natural Science Foundation of China (31970708, 82002953, 32170778, 82004177, 82072567), Shanghai Frontier Research Base of Disease and Syndrome Biology of Inflammatory cancer transformation (2021KJ03-12), National Scientific and Technological Major Special Project of China (2019ZX09201004-002-013), Tracking Program for Eastern Scholar at Shanghai Institutions of Higher Learning, Shanghai High-level Talent Leadership Program of Traditional Chinese Medicine [ZY(2021-2023)-0403], Scientific Research Project of Industry Development Center of Shanghai University of Traditional Chinese Medicine (602076D), the grant from Nantong Health Commission (MA2021024), Shanghai “Science and Technology Innovation Action Plan” Medical Innovation Research Project-Shanghai Clinical Research Center of Traditional Chinese Medicine Oncology (21MC1930500), Shanghai 13th Five-Year Plan Key Specialty of Traditional Chinese Medicine Oncology (shslczdzk03701), Three-year Action Plan for Shanghai TCM Development and Inheritance Program [ZY(2021-2023)-0401], and Health Commission of Pudong New Area Health and Family Planning Scientific Research Project (PW2019E-1).",
year = "2024",
month = may,
doi = "10.1038/s41418-024-01285-7",
language = "English",
volume = "31",
pages = "558--573",
journal = "Cell Death and Differentiation",
issn = "1476-5403",
publisher = "Springer Nature",
number = "5",

}

RIS

TY - JOUR

T1 - Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma

AU - Jin, Xing

AU - Liu, Lei

AU - Liu, Dan

AU - Wu, Jia

AU - Wang, Congcong

AU - Wang, Siliang

AU - Wang, Fengying

AU - Yu, Guanzhen

AU - Jin, Xiaoxia

AU - Xue, Yu Wen

AU - Jiang, Dan

AU - Ni, Yan

AU - Yang, Xi

AU - Wang, Ming Song

AU - Wang, Zhi Wei

AU - Orlov, Yuriy L.

AU - Jia, Wei

AU - Melino, Gerry

AU - Liu, Ji Bin

AU - Chen, Wen Lian

N1 - This work was supported by the National Key R&D Program of China (2023YFC3503200, 2023YFC3503201, 2022YFC3500200, 2022YFC3500202), National Natural Science Foundation of China (31970708, 82002953, 32170778, 82004177, 82072567), Shanghai Frontier Research Base of Disease and Syndrome Biology of Inflammatory cancer transformation (2021KJ03-12), National Scientific and Technological Major Special Project of China (2019ZX09201004-002-013), Tracking Program for Eastern Scholar at Shanghai Institutions of Higher Learning, Shanghai High-level Talent Leadership Program of Traditional Chinese Medicine [ZY(2021-2023)-0403], Scientific Research Project of Industry Development Center of Shanghai University of Traditional Chinese Medicine (602076D), the grant from Nantong Health Commission (MA2021024), Shanghai “Science and Technology Innovation Action Plan” Medical Innovation Research Project-Shanghai Clinical Research Center of Traditional Chinese Medicine Oncology (21MC1930500), Shanghai 13th Five-Year Plan Key Specialty of Traditional Chinese Medicine Oncology (shslczdzk03701), Three-year Action Plan for Shanghai TCM Development and Inheritance Program [ZY(2021-2023)-0401], and Health Commission of Pudong New Area Health and Family Planning Scientific Research Project (PW2019E-1).

PY - 2024/5

Y1 - 2024/5

N2 - Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

AB - Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

KW - Animals

KW - Humans

KW - Mice

KW - Cell Line, Tumor

KW - Cell Proliferation/drug effects

KW - Esophageal Neoplasms/metabolism

KW - Esophageal Squamous Cell Carcinoma/metabolism

KW - Gene Expression Regulation, Neoplastic

KW - Methionine/metabolism

KW - Mice, Nude

KW - Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism

KW - Oncogenes

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85189340150&origin=inward&txGid=7ad617efb6bd4d9bd856fbd36ab28b1f

UR - https://www.mendeley.com/catalogue/06875dcb-e745-3556-9fc2-d3b9190dca05/

U2 - 10.1038/s41418-024-01285-7

DO - 10.1038/s41418-024-01285-7

M3 - Article

C2 - 38570607

VL - 31

SP - 558

EP - 573

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1476-5403

IS - 5

ER -

ID: 60553461