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ID 116517
著者
Nakasuka, Fumie Keio University|The University of Tokyo
Tabata, Sho Keio University|University of Cincinnati|Osaka University
Sakamoto, Takeharu The University of Tokyo|Kanazawa University
Hirayama, Akiyoshi Keio University
Ebi, Hiromichi Aichi Cancer Center Research Institute
Yamada, Tadaaki Kyoto Prefectural University of Medicine
Umetsu, Ko Keio University
Ohishi, Maki Keio University
Ueno, Ayano Keio University
Sugimoto, Masahiro Keio University|Tokyo Medical University
Yamada, Yasuhiro The University of Tokyo
Tomita, Masaru Keio University
Sasaki, Atsuo T. Keio University|University of Cincinnati|Brain Tumor Center at UC Gardner Neuroscience Institute
矢野, 聖二 Kanazawa University
Soga, Tomoyoshi Keio University
資料タイプ
学術雑誌論文
抄録
Epithelial–mesenchymal transition (EMT)—a fundamental process in embryogenesis and wound healing—promotes tumor metastasis and resistance to chemotherapy. While studies have identified signaling components and transcriptional factors responsible in the TGF-β-dependent EMT, whether and how intracellular metabolism is integrated with EMT remains to be fully elucidated. Here, we showed that TGF-β induces reprogramming of intracellular amino acid metabolism, which is necessary to promote EMT in non-small cell lung cancer cells. Combined metabolome and transcriptome analysis identified prolyl 4-hydroxylase α3 (P4HA3), an enzyme implicated in cancer metabolism, to be upregulated during TGF-β stimulation. Further, knockdown of P4HA3 diminished TGF-β-dependent changes in amino acids, EMT, and tumor metastasis. Conversely, manipulation of extracellular amino acids induced EMT-like responses without TGF-β stimulation. These results suggest a previously unappreciated requirement for the reprogramming of amino acid metabolism via P4HA3 for TGF-β-dependent EMT and implicate a P4HA3 inhibitor as a potential therapeutic agent for cancer.
掲載誌名
Communications Biology
ISSN
23993642
出版者
Springer Nature
4
開始ページ
782
発行日
2021-06-24
権利情報
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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出版社版DOI
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フルテキストファイル
cb_4_782.pdf 3.07 MB
言語
eng
著者版フラグ
出版社版
部局
医学系