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| Status |
Public on Nov 06, 2019 |
| Title |
LSD1 mediates AKT activity in PIK3CA mutant colorectal cancer [RNA-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Activation of the epithelial-mesenchymal transition (EMT) program is a critical mechanism for initiating cancer progression and migration. Colorectal cancers (CRCs) contain many genetic and epigenetic alterations that can contribute to EMT. Mutations activating the PI3K/AKT signaling pathway are observed in >40% of patients with CRC contributing to increased invasion and metastasis. Little is known about how oncogenic signaling pathways such as PI3K/AKT synergize with chromatin modifiers to activate the EMT program. Lysine Specific Demethylase 1 (LSD1) is a chromatin-modifying enzyme that is overexpressed in colorectal cancer (CRC) and enhances cell migration. In this study we determine that LSD1 expression is significantly elevated in CRC patients with mutation of the catalytic subunit of PI3K, PIK3CA, compared to CRC patients with WT PIK3CA. LSD1 enhances activation of the AKT kinase in CRC cells through a non-catalytic mechanism, acting as a scaffolding protein for the transcription-repressing CoREST complex. Additionally, growth of PIK3CA mutant CRC cells is uniquely dependent on LSD1. Knockdown or CRISPR knockout of LSD1 blocks AKT-mediated stabilization of the EMT-promoting transcription factor Snail and effectively blocks AKT-mediated EMT and migration. Overall we uniquely demonstrate that LSD1 mediates AKT activation in response to growth factors and oxidative stress, and LSD1-regulated AKT activity promotes EMT-like characteristics in a subset of PIK3CA mutant cells.
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| Overall design |
RNA sequencing profiles were generated for LSD1 knockdown and GSK-LSD1 treated SW480 cells as well as LSD1 knockdown in HT29 cells compared to controls.
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| Contributor(s) |
O'Hagan HM, Miller SA |
| Citation(s) |
31704733 |
| |
| Submission date |
Nov 05, 2019 |
| Last update date |
Feb 07, 2020 |
| Contact name |
Robert Policastro |
| Organization name |
Ensoma Inc.
|
| Street address |
451 D St Unit #600
|
| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02210 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE139927 |
LSD1 mediates AKT activity in PIK3CA mutant colorectal cancer |
|
| Relations |
| BioProject |
PRJNA587642 |
| SRA |
SRP228574 |
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