Project description: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.
Project description:Although BRD8 has been considered to act as a coactivator of the NuA4/TIP60-histone acetyltransferase complex, the role of BRD8 in colorectal cancer cells remains to be elucidated. We performed transcriptome analysis to identify BRD8- and TIP60-regulated genes in colorectal cancer cells.
Project description:The first step in the development of human colorectal cancer (CRC) is the aberrant hyperactivation of the Wnt signaling pathway, predominantly caused by inactivating mutations in the adenomatous polyposis coli (APC) gene encoding an essential tumor suppressor. In order to identify genes affected by Apc loss, expression profiling of intestinal epithelium isolated from mice harboring the conditional allele of the gene was performed. The gene encoding transcriptional factor msh homeobox 1 (Msx1) displayed robust upregulation upon Apc inactivation. Subsequently, the expression pattern of human MSX1 was examined in a collection of colonic tumors. The MSX1 mRNA level was increased in all types of human intestinal neoplasia tested. In order to identify genes affected by MSX1 loss, expression profiling of human colorectal cancer cells SW620 upon MSX1 gene depletion was performed.