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Series GSE186785 Query DataSets for GSE186785
Status Public on Aug 23, 2022
Title Bacteria modulate tamoxifen-induced death via host fatty acid metabolism
Organism Caenorhabditis elegans
Experiment type Expression profiling by high throughput sequencing
Summary Our microbiota affects numerous processes involved in development, health, and the response to chemotherapeutic drugs. Tamoxifen is a selective estrogen receptor (ER) modulator that is used to treat ER positive breast cancer, but that at high doses kills both ER positive and ER-negative breast cancer cells. We recapitulate this off-target effect in Caenorhabditis elegans, which does not have an ER ortholog. We find that different bacteria dramatically modulate tamoxifen toxicity in C. elegans, with a three-order of magnitude difference between animals fed Escherichia coli, Comamonas aquatica, and Bacillus subtilis. Remarkably, host fatty acid (FA) biosynthesis mitigates tamoxifen toxicity, and different bacteria provide the animal with different FAs, resulting in distinct FA profiles. Surprisingly these bacteria modulate tamoxifen toxicity by different death mechanisms, some of which are modulated by FA supplementation and others by antioxidants. Together, this work reveals a complex interplay between bacteria, FA metabolism and tamoxifen toxicity that may provide a blueprint for similar studies in more complex mammals.
Overall design C. elegans RNA-sequencing of three experiments. Animals were treated with 400 µM citrate or 400 µM tamoxifen for 48 hours in biological triplicate.
Contributor(s) Diot C, Walhout AJ
Citation(s) 36151093
Submission date Oct 28, 2021
Last update date Oct 26, 2022
Contact name Hefei Zhang
Phone 5083040127
Organization name University of Massachusetts Chan Medical School
Department Department of Systems Biology
Lab Albertha,J,Walhout
Street address 4 Miles Ave
City Worcester
State/province Massachusetts
ZIP/Postal code 01545
Country USA
Platforms (1)
GPL30091 DNBSEQ-G400 (Caenorhabditis elegans)
Samples (5)
GSM5660990 Wild_type-48h-HT115-400uM_citrate-1
GSM5660991 Wild_type-48h-HT115-400uM_citrate-2
GSM5660992 Wild_type-48h-HT115-400uM_tamoxifen-1
BioProject PRJNA776017
SRA SRP343657

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Supplementary file Size Download File type/resource
GSE186785_citrate_tamoxifen_TPM.txt.gz 380.8 Kb (ftp)(http) TXT
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