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| Status |
Public on Mar 13, 2024 |
| Title |
Cytoplasmic localization of SETDB1 induced Warburg effect via c-MYC/ LDHA axis to enhance migration and invasion in breast carcinoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
SETDB1, a pivotal histone lysine methyltransferase, has been identified as being transported to the cytoplasm through a CMR1-dependent pathway, contributing to non-histone methylation. However, the function and underlying mechanism of cytoplasmic SETDB1 in breast cancer remain elusive. This study, employing immunohistochemistry, revealed that an elevated level of cytoplasmic SETDB1 is correlated with lymph node metastasis and more aggressive breast cancer subtypes. Functionally, cytoplasmic SETDB1 proves indispensable for cell migration and invasion, as well as the induction of epithelial-mesenchymal transition (EMT), which could be reversed by LMB (a CMR1 inhibitor) treatment. Furthermore, it was observed that cytoplasmic SETDB1 elevates the levels of metabolites associated with the Warburg effect, including glucose, pyruvate, lactate, and ATP. Mechanistically, the release of nuclear SETDB1 alleviates the inhibition of c-MYC transcription, leading to increased c-MYC expression and subsequent up-regulation of LDHA expression. Notably, LDHA overexpression enhanced migration and invasion by inducing EMT, while its depletion can reverse SETDB1-induced migration and invasion, as well as the Warburg effect and EMT. In conclusion, the subcellular localization of cytoplasmic SETDB1 emerges as a pivotal factor in breast cancer progression. This study offers valuable insights into the novel functions and mechanisms of cytoplasmic SETDB1.
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| Overall design |
MCF7/NC cells were treated with DMSO, MCF7/SETDB1 cells were treated with DMSO or LMB
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| Citation(s) |
38426579 |
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| Submission date |
Jan 19, 2024 |
| Last update date |
Mar 13, 2024 |
| Contact name |
Wenlin Yang |
| E-mail(s) |
wlyang1989@gmail.com
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| Phone |
8618605373007
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| Organization name |
Nantong Tumor Hospital Affiliated to Nantong University
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| Department |
Department of Pathology
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| Street address |
No.30, Tongyang North Road, Tongzhou District, Nantong, Jiangsu 226006, P.R. China
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| City |
Nantong |
| ZIP/Postal code |
226006 |
| Country |
China |
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| Platforms (1) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA1066816 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE253717_All_samples.GeneExpression.FPKM.txt.gz |
303.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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