Effect of asparagine depletion on Rspo3 fusion positive colorectal cancer cell organoid transcriptomes
Amino acid availability is a crucial factor for survivability of cancer cells. Colorectal cancer cells have been shown to resist asparagine depletion by utilizing GSK3-dependent proteasomal degradation, termed Wnt-dependent stabilization of proteins (Wnt/STOP), to replenish their amino acid pool. Inhibition of GSK3a halts the sourcing of amino acids, which subsequently leads to cancer cell vulnerability towards asparaginase therapy. Leveraging RNA sequencing we show that GSK3a inhibition leads to a significant enrichment of ribosomal transcripts amongst transcripts that are differentially downregulated in asparaginase treated Rspo3 fusion positive colorectal cancer cell organoids. Overall design: The effect of asparagine depletion on gene expression in Rspo3 fusion positive colorectal cancer cell organoids was investigated. Transcriptomes of vehicle and asparaginase treated organoids were sequenced and gene expression levels compaired.