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| Status |
Public on Apr 15, 2019 |
| Title |
Lamin B1 loss promotes lung cancer development and metastasis by epigenetic derepression of RET [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Although abnormal nuclear structure is an important criterion for cancer diagnostics, remarkably little is known about its relationship to tumor development. Here we report that loss of lamin B1, a determinant of nuclear architecture, plays a key role in lung cancer. We found that lamin B1 levels were reduced in lung cancer patients. Lamin B1 silencing in lung epithelial cells promoted epithelial-mesenchymal transition, cell migration, tumor growth and metastasis. Mechanistically, we show that lamin B1 recruits the polycomb repressive complex 2 (PRC2) to alter the H3K27me3 landscape and repress genes involved in cell migration and signaling. In particular, epigenetic derepression of the RET proto-oncogene by loss of PRC2 recruitment, and activation of the RET/p38 signaling axis, play a crucial role in mediating the malignant phenotype upon lamin B1 disruption. Importantly, loss of a single lamin B1 allele induced spontaneous lung tumor formation and RET activation. Thus, lamin B1 acts as a tumor suppressor in lung cancer, linking aberrant nuclear structure and epigenetic patterning with malignancy.
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| Overall design |
RNA-seq analysis of control (n=2; Lmnb1_ctrl_MLE12_RNA_seq_rep1 and Lmnb1_ctrl_MLE12_RNA_seq_rep2) and lamin B1 knockdown (n=2; Lmnb1_KD_MLE12_RNA_seq_rep1 and Lmnb1_KD_MLE12_RNA_seq_rep2) MLE12 cells.
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| Contributor(s) |
Jia Y, Cordero J, Dobreva G |
| Citation(s) |
31015297 |
| |
| Submission date |
Feb 08, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Gergana Dobreva |
| E-mail(s) |
[email protected]
|
| Organization name |
Medical Faculty Mannheim/University of Heidelberg
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| Department |
Cardiovascular Genomics and Epigenomics
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| Lab |
AG Dobreva
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| Street address |
Ludolf-Krehl-Str. 7-11
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| City |
Mannheim |
| State/province |
Baden Württemberg |
| ZIP/Postal code |
68167 |
| Country |
Germany |
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| Platforms (1) |
| GPL18635 |
Ion Torrent Proton (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE94681 |
Lamin B1 loss promotes lung cancer development and metastasis by epigenetic derepression of RET |
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| Relations |
| BioProject |
PRJNA371805 |
| SRA |
SRP099064 |
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