biostudies-literatureZhang JMOH | National Medical Research CouncilAgency for Science, Technology and ResearchNational Research Foundation Singapore2439https://www.ebi.ac.uk/biostudies/studies/S-EPMC10147683biostudies-literatureUnknown14(1)Cancer cells undergo transcriptional reprogramming to drive tumor progression and metastasis. Using cancer cell lines and patient-derived tumor organoids, we demonstrate that loss of the negative elongation factor (NELF) complex inhibits breast cancer development through downregulating epithelial-mesenchymal transition (EMT) and stemness-associated genes. Quantitative multiplexed Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (qPLEX-RIME) further reveals a significant rewiring of NELF-E-associated chromatin partners as a function of EMT and a co-option of NELF-E with the key EMT transcription factor SLUG. Accordingly, loss of NELF-E leads to impaired SLUG binding on chromatin. Through integrative transcriptomic and genomic analyses, we identify the histone acetyltransfeNature communicationsDependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis.PMC10147683UIBRNRF-CRP26-2021-0001NMRC-OFIRG21nov-0027NRF-NRFF2016-06NMRC-OFIRG21jun-0101Chen BJZhang JHu ZYeo CJSobota RMRaju ASou IFLakshmanan MTan EYTam WLTee WWLeong HFKang JLim YTRajarethinam RTan DEKPathak EVaiyapuri TSChung HHLau KWMcClurg ULTergaonkar VTian YWong ESMSer ZTan SYXfalseDependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis.Cancer cells undergo transcriptional reprogramming to drive tumor progression and metastasis. Using cancer cell lines and patient-derived tumor organoids, we demonstrate that loss of the negative elongation factor (NELF) complex inhibits breast cancer development through downregulating epithelial-mesenchymal transition (EMT) and stemness-associated genes. Quantitative multiplexed Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (qPLEX-RIME) further reveals a significant rewiring of NELF-E-associated chromatin partners as a function of EMT and a co-option of NELF-E with the key EMT transcription factor SLUG. Accordingly, loss of NELF-E leads to impaired SLUG binding on chromatin. Through integrative transcriptomic and genomic analyses, we identify the histone acetyltransfe2023-01-01T00:00:00Z2023 Apr2026-05-28T11:56:38.213Z2025-02-19T02:26:23.259ZS-EPMC101476833711718010.1038/s41467-023-38132-1