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Series GSE168875 Query DataSets for GSE168875
Status Public on Sep 21, 2023
Title A novel breast cancer therapeutic strategy through Hsp90 inhibition and activation of the immune system
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Low response rates and immune-related adverse events limit the impact of cancer immunotherapy. In the quest for improved clinical outcomes, preclinical studies have shown that combining immune checkpoint blockade therapies with N-terminal Hsp90 inhibitors resulted in improved efficacy, even though induction of an extensive heat shock response (HSR) with these inhibitors limited their clinical efficacy as monotherapies. We discovered that Enniatin A (EnnA) binds to the interface between the middle domains of the Hsp90 dimer and destabilizes Hsp90 client oncoproteins without inducing an HSR. We found that EnnA induces cancer cell immunogenic cell death in aggressive breast cancer models and exhibits superior anti-tumor activity compared to Hsp90 N-terminal inhibitors. Further, we show that EnnA reprograms the tumor microenvironment in syngeneic mouse models to promote CD8+ T cell-dependent anti-tumor activity mediated through the CX3CR1 signaling pathway. We propose that EnnA is a promising anti-tumor agent with a novel mechanism of action involving immunogenic cancer cell toxicity and the mobilization of CD8+ T cells into the tumor site.
Overall design Examination of the impact of Enniatin A (EnnA) and 17-AAG treatment on the transcriptome of murine breast cancer cell line E0771.
Contributor(s) Chadli A, Eisa N
Citation(s) 38025772
Submission date Mar 14, 2021
Last update date Dec 08, 2023
Contact name Ahmed Chadli
Phone 7067214661
Organization name Augusta University
Department Cancer Center
Street address 1410 Laney Walker BLVD
City Augusta
State/province GA
ZIP/Postal code 30912
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (6)
GSM5171796 E0771-DMSO1_S6
GSM5171797 E0771-DMSO2_S4
GSM5171798 E0771-EnnA1_S3
BioProject PRJNA714405
SRA SRP310562

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Supplementary file Size Download File type/resource
GSE168875_17AAG1_2_DMSO1_2.gene_exp.diffM.xlsx 902.5 Kb (ftp)(http) XLSX
GSE168875_EnnA1_2_DMSO1_2.gene_exp.diffM.xlsx 867.1 Kb (ftp)(http) XLSX
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