Showing papers by "Eric R. Fearon published in 2014"
TL;DR: It is shown that IL-17RA signals directly within transformed colonic epithelial cells (enterocytes) to promote early tumor development and is established as a therapeutic targets in colorectal cancer.
251 citations
TL;DR: The AXIN1 and AXIN2 sequence alterations reported in gastrointestinal cancers are reviewed, with the goal of vetting the evidence that some of the variants may have key functional roles in cancer development.
107 citations
TL;DR: It is reported for the first time that PRPF6, a member of the tri-snRNP (small ribonucleoprotein) spliceosome complex, drives cancer proliferation by preferential splicing of genes associated with growth regulation.
Abstract: The spliceosome machinery is composed of multimeric protein complexes that generate a diverse repertoire of mRNA through coordinated splicing of heteronuclear RNAs. While somatic mutations in spliceosome components have been discovered in several cancer types, the molecular bases and consequences of spliceosome aberrations in cancer are poorly understood. Here we report for the first time that PRPF6, a member of the tri-snRNP (small ribonucleoprotein) spliceosome complex, drives cancer proliferation by preferential splicing of genes associated with growth regulation. Inhibition of PRPF6 and other tri-snRNP complex proteins, but not other snRNP spliceosome complexes, selectively abrogated growth in cancer cells with high tri-snRNP levels. High-resolution transcriptome analyses revealed that reduced PRPF6 alters the constitutive and alternative splicing of a discrete number of genes, including an oncogenic isoform of the ZAK kinase. These findings implicate an essential role for PRPF6 in cancer via splicing of distinct growth-related gene products.
85 citations
TL;DR: Gene expression and metabolomic profiles of urine and tissue samples from mice with colorectal tumors and of coloreCTal tumor samples from patients revealed pathways associated with derangement of specific metabolic pathways that are indicative of early-stage tumor development.
74 citations
16 citations