|
| Status |
Public on Jan 11, 2018 |
| Title |
The role of LSD1 in Epithelial to Mesenchymal Transition |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs. LSD1 phosphorylation at serine-111 (LSD1-s111p) by chromatin anchored protein kinase C-theta (PKC-θ), is critical for its demethylase and EMT promoting activity and LSD1-s111p is enriched in chemoresistant cells in vivo. LSD1 couples to PKC-θ on the mesenchymal gene epigenetic template promotes LSD1-mediated gene induction. In vivo, chemotherapy reduced tumour volume, and when combined with an LSD1 inhibitor, abrogated the mesenchymal signature and promoted an innate, M1 macrophage-like tumouricidal immune response. Circulating tumour cells (CTCs) from metastatic breast cancer (MBC) patients were enriched with LSD1 and pharmacological blockade of LSD1 suppressed the mesenchymal and stem-like signature in these patient-derived CTCs. Overall, LSD1 inhibition may serve as a promising epigenetic adjuvant therapy to subvert its pleiotropic roles in breast cancer progression and treatment resistance.
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| |
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| Overall design |
4 treatments (mock siRNA and LSD1 siRNA with or without PMA and TGF). 1 replicate each
|
| |
|
| Contributor(s) |
Hardy K, Zafar A, Rao S |
| Citation(s) |
29311580 |
| Submission date |
Oct 10, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Kristine Hardy |
| E-mail(s) |
kristine.hardy@anu.edu.au
|
| Organization name |
University of Canberra
|
| Lab |
Cytokine Gene Expression
|
| Street address |
University of Canberra
|
| City |
Bruce |
| State/province |
ACT |
| ZIP/Postal code |
0200 |
| Country |
Australia |
| |
|
| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
|
| Samples (4)
|
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| This SubSeries is part of SuperSeries: |
| GSE104755 |
The role of LSD1 in Epithelial to Mesenchymal Transition: gene expression profiling and ChIP-seq |
|
| Relations |
| BioProject |
PRJNA413779 |
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