PXD031304
PXD031304 is an original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: NELF, breast cancer, EMT, qPLEX-RIME, TMT |
Contact List
Wee Wei Tee | |
---|---|
lab head | |
Radoslaw Sobota | |
contact affiliation | IMCB A-STAR Singapore |
dataset submitter |
Full Dataset Link List
jPOST dataset URI |
Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.jpostdb.org/JPST001463/ |