TGF-β-dependent reprogramming of amino acid metabolism induces epithelial–mesenchymal transition in non-small cell lung cancers

• Nakasuka, Fumie

• Tabata, Sho

• Sakamoto, Takeharu

• Hirayama, Akiyoshi

• Ebi, Hiromichi

• Yamada, Tadaaki

• Umetsu, Ko

• Ohishi, Maki

• Ueno, Ayano

• Goto, Hisatsugu

• Sugimoto, Masahiro

• Nishioka, Yasuhiko

• Yamada, Yasuhiro

• Tomita, Masaru

• Sasaki, Atsuo T.

• Yano, Seiji

• Soga, Tomoyoshi

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.

収録刊行物

• Communications Biology

  Communications Biology 4 782-, 2021-06-24

  Springer Nature

キーワード

• General Agricultural and Biological Sciences
• General Biochemistry, Genetics and Molecular Biology
• Medicine (miscellaneous)

詳細情報

• CRID: 1050008998076980224
• NII論文ID: 120007178465
• ISSN: 23993642
• DOI: 10.1038/s42003-021-02323-7
• Web Site: http://repo.lib.tokushima-u.ac.jp/116517
• Web Site: https://www.nature.com/articles/s42003-021-02323-7.pdf
• Web Site: https://www.nature.com/articles/s42003-021-02323-7
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN