Tumor cells have an increased need for amino acids. Mammalian cells cannot synthesize essential amino acids; they must obtain these amino acids via specific transporters. Glutamine, though a non-essential amino acid, is critical for tumor cells (glutamine addiction). Entry of amino acids into tumor cells is enhanced by upregulation of specific transporters. If the transporters that are specifically induced in tumor cells are identified, blockade of the induced transporters would constitute a logical strategy for cancer treatment.
Deletion of the amino acid transporter Slc6a14 suppresses tumour growth in spontaneous mouse models of breast cancer.
Age, Specimen part
View SamplesMicroarray gene expression profiling reveals that PHGDH inhibition by NCT-503 activates a metabolic stress response characterized by downregulation of cell cycle genes and induction of stress response genes.
Metabolic Reprogramming by MYCN Confers Dependence on the Serine-Glycine-One-Carbon Biosynthetic Pathway.
Specimen part, Cell line
View SamplesIxodes species ticks are competent vectors of tick-borne viruses including tick-borne encephalitis and Powassan encephalitis. Tick saliva has been shown to facilitate and enhance viral infection. This likely occurs by saliva-mediated modulation of host responses into patterns favorable for viral infection and dissemination. Because of the rapid kinetics of tick-borne viral transmission, this modulation must occur as early as tick attachment and initiation of feeding. In this study, the gene expression profile of cutaneous bite-site lesions created by uninfected ticks were analyzed at 1, 3, 6, and 12 hours after Ixodes scapularis nymphal tick attachment to discover host pathways or responses potentially important in tick-borne viral establishment.
Early immunologic events at the tick-host interface.
Specimen part, Time
View SamplesThe purpose of this study was to determine and clarify the retinoic effect on the gene expression profile for mouse dendritic cells.
Retinoic acid promotes the development of Arg1-expressing dendritic cells for the regulation of T-cell differentiation.
Specimen part
View SamplesThe LXCXE peptide motif facilitates interaction between the RB tumor suppressor and a large number of cellular proteins that are expected to impinge on diverse biological processes. In vitro and in vivo analyses demonstrated that LXCXE-binding function is dispensable for RB promoter association and control of basal gene expression. Dependence on this function of RB is unmasked after DNA damage, wherein LXCXE-binding is essential for exerting control over E2F3 and suppressing cell cycle progression in the presence of genotoxic stress. Gene expression profiling revealed that the transcriptional program coordinated by this specific aspect of RB is associated with progression of human hepatocellular carcinoma and poor disease outcome. Consistent with these findings, biological challenge revealed a requirement for LXCXE-binding in suppression of genotoxin-initiated hepatocellular carcinoma in vivo. Together, these studies establish an essential role of the LXCXE-binding motif for RB-mediated transcriptional control, response to genotoxic insult, and tumor suppression.
RB restricts DNA damage-initiated tumorigenesis through an LXCXE-dependent mechanism of transcriptional control.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.
Specimen part, Disease, Disease stage
View SamplesType II Enteropathy-associated T-cell lymphoma (Type II EATL) is an aggressive intestinal T-cell lymphoma with poor prognosis and has not been molecularly profiled. Through targeted amplicon sequencing, we identified a large portion of Type II EATL samples that harbor mutations in the STAT5B, JAK3 and GNAI2 genes. Here we performed gene expression profiling on four Type II EATL samples in order to better characterize this disease. As Type II EATL is suggested to arise from CD8+ IELs, we integrated our data with publicly available profile of CD8 and CD8 T-cells from healthy donors (GSE33374). Gene expression profiling independently demonstrated strong enrichment of several aspects of GPCR and JAK-STAT signaling pathways. Moreover, an significant association was identified with genes containing STAT5B binding sites in their promoters.
JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis.
Disease stage
View SamplesCell surface sialylation confers many roles in cancer biology including cell proliferation, invasiveness, metastasis and angiogenesis. We show here that ST3Gal1 sialyltransferase marks a self-renewing cellular fraction. Depletion of ST3GAL1 abrogates glioma cell growth and tumorigenicity. In contrast, TGFb induces ST3GAL1 expression and correlates with the pattern of ST3Gal1 activation in patient tumors of the mesenchymal molecular subtype. To delineate the downstream events of ST3Gal1 signaling, we utilized a bioinformatical approach that leveraged on the greater statistical power of large patient databases, and subsequently verified our predictions in patient-derived glioma cells. We identify FoxM1, a major stem cell regulatory gene, as a downstream effector, and show that ST3Gal1 mediates the glioma phenotype through control of FoxM1 protein degradation
ST3GAL1-Associated Transcriptomic Program in Glioblastoma Tumor Growth, Invasion, and Prognosis.
Disease stage
View SamplesCDk4/6 inhibitor activates RB and represses RB/E2F target genes
RB Loss Promotes Prostate Cancer Metastasis.
Cell line, Treatment
View Samples