{"doi":"10.1038/s42003-021-02323-7","title":"TGF-β-dependent reprogramming of amino acid metabolism induces epithelial–mesenchymal transition in non-small cell lung cancers","abstract":"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.","journal":"Communications Biology","year":2021,"id":156511,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":54,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":661506,"name":"Sho Tabata","orcid":"0000-0001-8956-9241","position":1,"is_corresponding":false},{"id":661507,"name":"Takeharu Sakamoto","orcid":"0000-0002-1225-1902","position":2,"is_corresponding":false},{"id":504904,"name":"Akiyoshi Hirayama","orcid":"0000-0002-0440-6820","position":3,"is_corresponding":false},{"id":318500,"name":"Hiromichi Ebi","orcid":"0000-0003-3155-7576","position":4,"is_corresponding":false},{"id":661508,"name":"Tadaaki Yamada","orcid":"0000-0002-6945-281X","position":5,"is_corresponding":false},{"id":662505,"name":"Ko Umetsu","orcid":null,"position":6,"is_corresponding":false},{"id":662506,"name":"Maki Ohishi","orcid":null,"position":7,"is_corresponding":false},{"id":662507,"name":"Ayano Ueno","orcid":null,"position":8,"is_corresponding":false},{"id":662508,"name":"Hisatsugu Goto","orcid":null,"position":9,"is_corresponding":false},{"id":661509,"name":"Masahiro Sugimoto","orcid":"0000-0003-3316-2543","position":10,"is_corresponding":false},{"id":648456,"name":"Yasuhiko Nishioka","orcid":"0000-0001-6311-1654","position":11,"is_corresponding":false},{"id":661510,"name":"Yasuhiro Yamada","orcid":"0000-0002-2463-1478","position":12,"is_corresponding":false},{"id":29264,"name":"Masaru Tomita","orcid":"0000-0003-3423-377X","position":13,"is_corresponding":false},{"id":351874,"name":"Atsuo T. Sasaki","orcid":"0000-0003-2963-4501","position":14,"is_corresponding":false},{"id":661511,"name":"Seiji Yano","orcid":"0000-0002-6151-2988","position":15,"is_corresponding":false},{"id":504908,"name":"Tomoyoshi Soga","orcid":"0000-0001-9502-2509","position":16,"is_corresponding":false},{"id":661505,"name":"Fumie Nakasuka","orcid":"0000-0001-8549-2769","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-18T23:44:13.017332Z","pmid":"34168290","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}