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Series GSE219133 Query DataSets for GSE219133
Status Public on Jan 01, 2023
Title Wnt inhibitors reduce the unfolded protein response and enhance bortezomib-induced cell death in multiple myeloma
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Dysregulation of the Wnt pathway is involved in pathogenesis of many types of carcinomas and associated with certain hematological cancers, including multiple myeloma (MM). Several studies reported that MM plasma cells carry a functional Wnt/β-catenin signaling pathway that promotes cell survival. Despite new and successful treatment options, MM remains incurable due to clinical, genetic and transcriptomic heterogeneity, which ultimately results in therapy resistance and relapse. We examined the therapeutic potential of targeting the Wnt pathway in patient-derived MM cells. Our results demonstrate that inhibition of tankyrase (TNKSi) and inhibition of porcupine (PORCi), two established methods to block the Wnt pathway in other cell types and malignancies, promotes cell death of primary MM cells. Single-cell RNA sequencing showed that inhibition of Wnt signaling is likely effectuated via downregulation of genes involved in the unfolded protein response (UPR). Combining TNKSi and PORCi with bortezomib resulted in a potent killing of primary MM cells, demonstrating that inhibitors of Wnt signaling might be considered as therapeutic targets in future anti-myeloma combinatorial strategies.
 
Overall design Transcriptome analysis by single-cell RNA sequencing of viable CD38+CD138+ primary MM cells of samples MM09-MM13 after 72 hours of exposure to a combination of 20 μM tankyrase inhibitor (TNKSi) XAV939 and 5 μM porcupine inhibitor C59, or untreated control cells, in the presence of IL-6 and APRIL.
 
Contributor(s) Peperzak V, Spaan I, van Nieuwenhuijzen N
Citation(s) 36459495
Submission date Dec 01, 2022
Last update date Feb 23, 2023
Contact name Victor Peperzak
E-mail(s) v.peperzak@umcutrecht.nl
Organization name UMC Utrecht
Department Center for Translational Immunology
Lab Peperzak lab
Street address Heidelberglaan 100
City Utrecht
State/province Utrecht
ZIP/Postal code 3584 CX
Country Netherlands
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (10)
GSM6774436 Sample MM09 control (s019)
GSM6774437 Sample MM09 +WNTi (s020)
GSM6774438 Sample MM10 control (s021)
Relations
BioProject PRJNA907219

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE219133_RAW.tar 30.6 Mb (http)(custom) TAR (of PDF, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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