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| Status |
Public on Apr 01, 2019 |
| Title |
RNA-seq of MDA-MB-231 siCt and siAXL |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Triple-Negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is associated with poor prognosis due to its propensity to form metastases. Unfortunately, the current treatment options are limited to chemotherapy such that identification of actionable targets are needed. The receptor tyrosine kinase AXL plays a role in the tumor cell dissemination and its expression in TNBC correlates with poor patients? survival. Here, we explored whether exploiting an AXL knockdown gene signature in TNBC cells may offer an opportunity for drug repurposing. To this end, we queried the PharmacoGx pharmacogenomics platform with an AXL gene signature which revealed Phenothiazines, a class of Dopamine Receptors antagonists (Thioridazine, Fluphenazine and Trifluoperazine) typically used as anti-psychotics. We next tested if drugs may be active to limit growth and metastatic progression of TNBC cells, similarly to AXL depletion. We found that the Phenothiazines were able to reduce cel l invasion, proliferation and viability, and also increased apoptosis of TNBC cells in vitro. Mechanistically, these drugs did not affect AXL activity but instead reduced PI3K/AKT/mTOR and ERK signaling. When administered to mice bearing TNBC xenografts, these drugs showed were able to reduce tumor growth and metastatic burden. Collectively, these results suggest that these antipsychotics are novel anti-tumor and anti-metastatic agents that could potentially be repurposed, in combination with standard chemotherapy, for use in TNBC.
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| Overall design |
RNA-seq of the Triple Negative Breast Cancer cell line MDA-MB-231 treated with siCt or siAXL
Differential gene expression profile between MDA-MB-231 siCt and siAXL by RNA sequencing (Illumina HiSEq 2000)
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| Contributor(s) |
Côté J, Goyette M |
| Citation(s) |
31007848 |
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| Submission date |
Sep 20, 2018 |
| Last update date |
May 02, 2019 |
| Contact name |
Marie-Anne Goyette |
| Organization name |
IRCM
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| Street address |
110 av. Des Pins Ouest
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| City |
Montreal |
| ZIP/Postal code |
H2W 1R7 |
| Country |
Canada |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA492335 |
| SRA |
SRP162274 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE120268_deseq_differential_expression_results.txt.gz |
1.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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