Dysregulation of Wnt/TCF signaling is closely associated with cancers arising from the gastrointestinal tract, inlcluding colon cancer and liver cancer. The goal of this study is to understand the transcriptional programs underlying Wnt/TCF activation in gastrointestinal cancers. We examined the transcriptional responses to TCF inhibition in cultured human colon cancer cells and liver cancer cells that are characteristic of Wnt pathway activation.
TRIB2 acts downstream of Wnt/TCF in liver cancer cells to regulate YAP and C/EBPα function.
Cell line
View SamplesFoxA transcription factors are involved in development and tumorigenesis of the gastrointestinal tract. However, the downstream programs controlled by FoxA factors remain poorly understood. The goal of this study is to understand the transcriptional responses regulated by FoxA proteins in liver and colon cancer cells.
TRIB2 acts downstream of Wnt/TCF in liver cancer cells to regulate YAP and C/EBPα function.
Cell line
View SamplesPancreatic Ductal Adenocarcinoma (PDAC) is one of the most aggressive human malignancies. In our studies, we find that the Gli transcription factors are required for Kras initiation of pancreatic tumorigenesis. In order to identify the downstream transcriptional targets of Gli in PDAC, we conducted gene expression analysis using Gli3T, a transcriptional repressor of Gli.
The activity of Gli transcription factors is essential for Kras-induced pancreatic tumorigenesis.
Cell line
View SamplesTo understand the interplay between cancer and stroma, we performed single cell RNA-sequencing of PDAC cells admixed with stromal fibroblasts and defined different single cell populations with varying levels of proliferative and metastatic transcriptional states. PDAC cell behavior in vitro and in vivo on these phenotypic axes could be tuned with the proportion of stromal fibroblasts. These cell types were identified in human pancreatic tumors, and specific subpopulations were associated with worsened outcomes. Overall design: 92 single PDAC cells and 92 single CAF cells were micromanipulated and prepared for sequencing (23 of each cell type from four culture ratios). The 24th sample from each cell type-culture condition combination is a population control obtained by micromanipulating 100 cells of the given type from the given culture condition and preparing it as if it were a single cell, giving a total of 96 PDAC samples and 96 CAF samples. During the course of library construction, 3 samples were lost, all PDAC cells from the 30:70 condition (two single cells and the population control), leaving 93 total PDAC samples and 96 total CAF samples.
Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer.
Specimen part, Subject
View SamplesGlioblastoma multiforme (GBM) is the most malignant and most common tumor of the central nervous system characterized by rapid growth and extensive tissue infiltration. GBM results in more years of life lost than any other cancer type. Notch signaling has been implicated in GBM pathogenesis through several modes of action. Inhibition of Notch leads to a reduction of cancer-initiating cells in gliomas and reduces proliferation and migration. Deltex1 (DTX1) is part of an alternative Notch signaling pathway distinct from the canonical MAML1/RBPJ-mediated cascade. In this study, we show that DTX1 activates both the RTK/PI3K/PKB as well as the MAPK/ERK pathway. Moreover, we found the anti-apoptotic factor Mcl-1 to be induced by DTX1. In accordance with this, the clonogenic potential and proliferation rates of glioma cell lines correlated with DTX1 levels. DTX1 knock down mitigated the tumorigenic potential in vivo, and overexpression of DTX1 increased cell migration and invasion of tumor cells accompanied by an elevation of the pro-migratory factors PKB and Snail1. Microarray gene expression analysis identified a DTX1-specific transcriptional program - including microRNA-21 - which is distinct from the canonical Notch signaling. We propose the alternative Notch pathway via DTX1 as oncogenic factor in malignant glioma and found low DTX1 expression levels to correlate with prolonged survival of GBM and early breast cancer patients in open source databases.
Deltex-1 activates mitotic signaling and proliferation and increases the clonogenic and invasive potential of U373 and LN18 glioblastoma cells and correlates with patient survival.
Specimen part, Cell line
View SamplesA cancer stem cell cannot be identified solely based on surface markers as none of the markers used to isolate stem cells in various normal and cancerous tissues is expressed exclusively by stem cells. Our experimental results have also identified additional fractions representing true stem-like cells in oral squamous cell carcinoma (OSCC), refuting the concept that cancer stem cells (CSCs) are a rare population, and we have also developed an in vitro model to explore the stem cell concept in oral epithelial tumorigenesis. This model expounds four distinct fractions within a homogenous cell line SCC172 that is morphologically similar (85% cells expressing CSC markers), yet varying in all functional aspects of cell cycle, dye retention, chemoresistance, tumor-forming potential, self renewal, apoptosis resistance and regulation at molecular levels. Relating to our CSC shift model, we analysed the concept of biological heterogeneity in terms of four fractions SP1, SP2, MP1 and MP2 and associated it with variations among patients in a clinical scenario.
Analysis of MicroRNA-mRNA Interactions in Stem Cell-Enriched Fraction of Oral Squamous Cell Carcinoma.
Specimen part, Cell line
View SamplesUsing a novel class of chemically-engineered oligonucleotides, termed "antagomirs", we studied the biological significance of silencing miR-122 in the liver of mice at the mRNA level
Silencing of microRNAs in vivo with 'antagomirs'.
No sample metadata fields
View SamplesThe goal of this study was to investigate DNA methylation and gene expression changes in a zebrafish model of ICF Syndrome which were generated by mutation of ICF-gene zbtb24. Comparison of gene expression changes between wildtype and zbtb24 homozygous mutants revealed upregulation of interferon response genes following zbtb24 deletion. Upregulation of interferon response genes was blocked by mutation of the dsRNA helicase Mda5. Overall design: For RNA-seq, gene expression was compared in whole two-week-old zebrafish larvae that were wildtype or homozygous for the zbtb24mk22 mutant allele. We further performed RNA-Seq analysis in three-week-old zebrafish larvae that were WT, mda5mk29/mk29 , zbtb24mk22/mk22 and mda5mk29/mk29 ;zbtb24mk22/mk22. Three samples consisting of pools of 10 larvae were examined for each genotype. For ERRBS, DNA was separately isolated from the fins of three wildtype and three zbtb24mk22 homozygous mutant adults.
Pericentromeric hypomethylation elicits an interferon response in an animal model of ICF syndrome.
Subject
View SamplesMost B cell lymphomas arise in the germinal center (GC), where humoral immune responses evolve from potentially oncogenic cycles of mutation, proliferation, and clonal selection. Although lymphoma gene expression diverges significantly from GC-B cells, underlying mechanisms that alter the activities of corresponding regulatory elements (REs) remain elusive. Here we define the complete pathogenic circuitry of human follicular lymphoma (FL), which activates or decommissions transcriptional circuits from normal GC-B cells and commandeers enhancers from other lineages. Moreover, independent sets of transcription factors, whose expression is deregulated in FL, target commandeered versus decommissioned REs. Our approach reveals two distinct subtypes of low-grade FL, whose pathogenic circuitries resemble GC-B or activated B cells. Remarkably, FL-altered enhancers also are enriched for sequence variants, including somatic mutations, which disrupt transcription factor binding and expression of circuit-linked genes. Thus, the pathogenic regulatory circuitry of FL reveals distinct genetic and epigenetic etiologies for GC-B transformation. Overall design: Expression profiles of follicular lymphoma, centrocyte and peripheral blood B cells were generated by deep sequencing, using Illumina Hi-Seq 2000.
NKG2D-NKG2D Ligand Interaction Inhibits the Outgrowth of Naturally Arising Low-Grade B Cell Lymphoma In Vivo.
No sample metadata fields
View Samplesthe molecular mechanisms for the biphasic effect of alcohol are not fully understood. The goal of the study is to identify genes that are differentially expressed following alcohol exposure of 50mM and 100mM ethanol for 24 hours.
Ethanol upregulates glucocorticoid-induced leucine zipper expression and modulates cellular inflammatory responses in lung epithelial cells.
No sample metadata fields
View Samples