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PHGDH preserves one-carbon cycle to confer metabolic plasticity in chemoresistant gastric cancer during nutrient stress
DC Field | Value | Language |
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dc.contributor.author | 김재우 | - |
dc.contributor.author | 윤보경 | - |
dc.contributor.author | 정재호 | - |
dc.contributor.author | 황성순 | - |
dc.date.accessioned | 2023-07-12T03:00:10Z | - |
dc.date.available | 2023-07-12T03:00:10Z | - |
dc.date.issued | 2023-05 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/195467 | - |
dc.description.abstract | Molecular classification of gastric cancer (GC) identified a subgroup of patients showing chemoresistance and poor prognosis, termed SEM (Stem-like/Epithelial-to-mesenchymal transition/Mesenchymal) type in this study. Here, we show that SEM-type GC exhibits a distinct metabolic profile characterized by high glutaminase (GLS) levels. Unexpectedly, SEM-type GC cells are resistant to glutaminolysis inhibition. We show that under glutamine starvation, SEM-type GC cells up-regulate the 3 phosphoglycerate dehydrogenase (PHGDH)-mediated mitochondrial folate cycle pathway to produce NADPH as a reactive oxygen species scavenger for survival. This metabolic plasticity is associated with globally open chromatin structure in SEM-type GC cells, with ATF4/CEBPB identified as transcriptional drivers of the PHGDH-driven salvage pathway. Single-nucleus transcriptome analysis of patient-derived SEM-type GC organoids revealed intratumoral heterogeneity, with stemness-high subpopulations displaying high GLS expression, a resistance to GLS inhibition, and ATF4/CEBPB activation. Notably, coinhibition of GLS and PHGDH successfully eliminated stemness-high cancer cells. Together, these results provide insight into the metabolic plasticity of aggressive GC cells and suggest a treatment strategy for chemoresistant GC patients. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | National Academy of Sciences | - |
dc.relation.isPartOf | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Glutamine / metabolism | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Nutrients | - |
dc.subject.MESH | Phosphoglycerate Dehydrogenase* / genetics | - |
dc.subject.MESH | Phosphoglycerate Dehydrogenase* / metabolism | - |
dc.subject.MESH | Stomach Neoplasms* / drug therapy | - |
dc.subject.MESH | Stomach Neoplasms* / genetics | - |
dc.title | PHGDH preserves one-carbon cycle to confer metabolic plasticity in chemoresistant gastric cancer during nutrient stress | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) | - |
dc.contributor.googleauthor | Bo Kyung Yoon | - |
dc.contributor.googleauthor | Hyeonhui Kim | - |
dc.contributor.googleauthor | Tae Gyu Oh | - |
dc.contributor.googleauthor | Se Kyu Oh | - |
dc.contributor.googleauthor | Sugyeong Jo | - |
dc.contributor.googleauthor | Minki Kim | - |
dc.contributor.googleauthor | Kyu-Hye Chun | - |
dc.contributor.googleauthor | Nahee Hwang | - |
dc.contributor.googleauthor | Suji Lee | - |
dc.contributor.googleauthor | Suyon Jin | - |
dc.contributor.googleauthor | Annette R Atkins | - |
dc.contributor.googleauthor | Ruth T Yu | - |
dc.contributor.googleauthor | Michael Downes | - |
dc.contributor.googleauthor | Jae-Woo Kim | - |
dc.contributor.googleauthor | Hyunkyung Kim | - |
dc.contributor.googleauthor | Ronald M Evans | - |
dc.contributor.googleauthor | Jae-Ho Cheong | - |
dc.contributor.googleauthor | Sungsoon Fang | - |
dc.identifier.doi | 10.1073/pnas.2217826120 | - |
dc.contributor.localId | A00865 | - |
dc.contributor.localId | A05928 | - |
dc.contributor.localId | A03717 | - |
dc.contributor.localId | A05443 | - |
dc.relation.journalcode | J02550 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.pmid | 37192160 | - |
dc.identifier.url | https://www.pnas.org/doi/10.1073/pnas.2217826120 | - |
dc.subject.keyword | 3 phosphoglycerate dehydrogenase | - |
dc.subject.keyword | gastric cancer | - |
dc.subject.keyword | glutaminase | - |
dc.subject.keyword | metabolic plasticity | - |
dc.contributor.alternativeName | Kim, Jae Woo | - |
dc.contributor.affiliatedAuthor | 김재우 | - |
dc.contributor.affiliatedAuthor | 윤보경 | - |
dc.contributor.affiliatedAuthor | 정재호 | - |
dc.contributor.affiliatedAuthor | 황성순 | - |
dc.citation.volume | 120 | - |
dc.citation.number | 21 | - |
dc.citation.startPage | e2217826120 | - |
dc.identifier.bibliographicCitation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.120(21) : e2217826120, 2023-05 | - |
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