PXD031304

PXD031304 is an original dataset announced via ProteomeXchange.

Title	Dependency of NELF-E-KAT2B epigenetic axis in breast cancer carcinogenesis
Description	Cancer cells undergo transcriptional reprogramming to drive tumor progression and metastasis. Here, we identified the transcriptional complex, NELF (Negative elongation factor), as an important regulator of this process. Using cancer cell lines and patient-derived tumor organoids, we demonstrated that loss of NELF inhibits breast cancer tumorigenesis and metastasis. Specifically, we found that epithelial-mesenchymal transition (EMT) and stemness-associated genes are downregulated in NELF-depleted breast cancer cells. Quantitative Multiplexed Rapid Immunoprecipitation Mass spectrometry of Endogenous proteins (qPLEX-RIME) of NELF-E, a key subunit of NELF, reveals significant rewiring of NELF-E-associated chromatin partners as a function of EMT, and further illuminates a co-option of NELF-E with the key EMT transcription factor SLUG. Accordingly, loss of NELF-E led to impaired SLUG binding on chromatin. Through integrative transcriptomic and genomic analyses, we identified the histone acetyltransferase, KAT2B, as a key functional target of NELF-E-SLUG. Genetic and pharmacological inactivation of KAT2B ameliorate expression of critical EMT marker genes, phenocopying NELF ablation. Elevated NELF-E and KAT2B expressions are associated with poorer prognosis in breast cancer patients, highlighting the clinical relevance of our findings. Importantly, KAT2B knockout mice are viable, raising the exciting prospect of targeting this dependency therapeutically. Taken together, we uncovered a crucial role of the NELF-E-KAT2B epigenetic axis in breast cancer carcinogenesis.
HostingRepository	jPOST
AnnounceDate	2023-01-28
AnnouncementXML	Submission_2023-11-22_23:26:40.220.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Radoslaw Sobota
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	L-methionine sulfoxide; S-carboxamidomethyl-L-cysteine; alpha-amino acetylated residue; unknown modification; unknown modification; deamidated L-asparagine; deamidated L-glutamine
Instrument	instrument

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-27 22:11:07	ID requested
1	2023-01-27 07:00:05	announced
⏵ 2	2023-11-22 23:26:41	announced	2023-11-23: Updated PubMed.

Zhang J, Hu Z, Chung HH, Tian Y, Lau KW, Ser Z, Lim YT, Sobota RM, Leong HF, Chen BJ, Yeo CJ, Tan SYX, Kang J, Tan DEK, Sou IF, McClurg UL, Lakshmanan M, Vaiyapuri TS, Raju A, Wong ESM, Tergaonkar V, Rajarethinam R, Pathak E, Tam WL, Tan EY, Tee WW, Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis. Nat Commun, 14(1):2439(2023) [pubmed]

submitter keyword: NELF, breast cancer, EMT, qPLEX-RIME, TMT

Wee Wei Tee
lab head
Radoslaw Sobota
contact affiliation	IMCB A-STAR Singapore
dataset submitter

jPOST dataset URI

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