A metabolic shift to the serine pathway induced by lipids fosters epigenetic reprogramming in nontransformed breast cells
dc.contributor.author | Eduardo, Mariana Bustamante | |
dc.contributor.author | Cottone, Gannon | |
dc.contributor.author | McCloskey, Curtis W. | |
dc.contributor.author | Liu, Shiyu | |
dc.contributor.author | Palma, Flavio R. | |
dc.contributor.author | Zappia, Maria Paula | |
dc.contributor.author | Islam, Abul B. M. M. K. | |
dc.contributor.author | Gao, Peng | |
dc.contributor.author | Setya, Joel | |
dc.contributor.author | Dennis, Saya | |
dc.contributor.author | Gao, Hongyu | |
dc.contributor.author | Zhang, Qian | |
dc.contributor.author | Xuei, Xiaoling | |
dc.contributor.author | Luo, Yuan | |
dc.contributor.author | Locasale, Jason | |
dc.contributor.author | Bonini, Marcelo G. | |
dc.contributor.author | Khokha, Rama | |
dc.contributor.author | Frolov, Maxim V. | |
dc.contributor.author | Benevolenskaya, Elizaveta V. | |
dc.contributor.author | Chandel, Navdeep S. | |
dc.contributor.author | Khan, Seema A. | |
dc.contributor.author | Clare, Susan E. | |
dc.contributor.department | Medical and Molecular Genetics, School of Medicine | |
dc.date.accessioned | 2025-04-21T09:14:49Z | |
dc.date.available | 2025-04-21T09:14:49Z | |
dc.date.issued | 2025 | |
dc.description.abstract | Lipid metabolism and the serine, one-carbon, glycine (SOG) and methionine pathways are independently and significantly correlated with estrogen receptor-negative breast cancer (ERneg BC). Here, we propose a link between lipid metabolism and ERneg BC through phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in the de novo serine pathway. We demonstrate that the metabolism of the paradigmatic medium-chain fatty acid octanoic acid leads to a metabolic shift toward the SOG and methionine pathways. PHGDH plays a role in both the forward direction, contributing to the production of S-adenosylmethionine, and the reverse direction, generating the oncometabolite 2-hydroxyglutarate, leading to epigenomic reprogramming and phenotypic plasticity. The methionine cycle is closely linked to the transsulfuration pathway. Consequently, we observe that the shift increases the antioxidant glutathione, which mitigates reactive oxygen species (ROS), enabling survival of a subset of cells that have undergone DNA damage. These metabolic changes contribute to several hallmarks of cancer. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Eduardo MB, Cottone G, McCloskey CW, et al. A metabolic shift to the serine pathway induced by lipids fosters epigenetic reprogramming in nontransformed breast cells. Sci Adv. 2025;11(12):eads9182. doi:10.1126/sciadv.ads9182 | |
dc.identifier.uri | https://hdl.handle.net/1805/47202 | |
dc.language.iso | en_US | |
dc.publisher | American Association for the Advancement of Science | |
dc.relation.isversionof | 10.1126/sciadv.ads9182 | |
dc.relation.journal | Science Advances | |
dc.rights | Attribution 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.source | PMC | |
dc.subject | Breast neoplasms | |
dc.subject | Phosphoglycerate dehydrogenase | |
dc.subject | Glutathione | |
dc.subject | Serine | |
dc.subject | Reactive oxygen species | |
dc.title | A metabolic shift to the serine pathway induced by lipids fosters epigenetic reprogramming in nontransformed breast cells | |
dc.type | Article |