Protein 4.1B is a 4.1/ezrin/radixin/moesin (FERM) domain-containing protein whose expression is frequently lost in a variety of human tumors, including meningiomas, non-small-cell lung cancers and breast carcinomas. However, its potential tumor suppressive function under in vivo conditions remains to be validated. In a screen for genes involved with prostate cancer metastasis, we found that 4.1B expression is reduced in highly metastatic tumors. Downregulation of 4.1B increased the metastatic propensity of poorly metastatic cells in an orthotopic model of prostate cancer. Furthermore, 4.1B-deficient mice displayed increased susceptibility for developing aggressive, spontaneous prostate carcinomas. In both cases, enhanced tumor malignancy was associated with reduced apoptosis. As expression of Protein 4.1B is frequently downregulated in human clinical prostate cancer, as well as in a spectrum of other tumor types, these results suggest a more general role for Protein 4.1B as a negative regulator of cancer progression to metastatic disease.
Protein 4.1B suppresses prostate cancer progression and metastasis.
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View SamplesNon-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. The oxygen-sensitive Hypoxia Inducible Factor (HIF) transcriptional regulators HIF-1 and HIF-2 are overexpressed in many human NSCLCs, and constitutive HIF-2 activity can promote murine lung tumor progression, suggesting that HIF proteins may be effective NSCLC therapeutic targets. To investigate the consequences of inhibiting HIF activity in lung cancers, we deleted Hif-1 or Hif-2 in an established KrasG12D-driven murine NSCLC model. Deletion of Hif-1 had no obvious effect on tumor growth, whereas Hif-2 deletion resulted in an unexpected increase in tumor burden that correlated with reduced expression of the candidate tumor suppressor gene Scgb3a1 (HIN-1).
HIF-2alpha deletion promotes Kras-driven lung tumor development.
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View SamplesTranslation is a critical cellular process to synthesize proteins from their transcripts. However, translational regulation in antigen-specific T cells in vivo has not been well defined.
Translation is actively regulated during the differentiation of CD8<sup>+</sup> effector T cells.
Sex, Specimen part
View SamplesTranscriptional profiling of an Fd-GOGAT1/GLU1 mutant in Arabidopsis thaliana reveals a multiple stress response and extensive reprogramming of the transcriptome
Transcriptional profiling of an Fd-GOGAT1/GLU1 mutant in Arabidopsis thaliana reveals a multiple stress response and extensive reprogramming of the transcriptome.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing.
Specimen part
View SamplesPRDM16 is a strong activator of brown fat-specific genes, while also a repressor of white fat and muscle-specific genes. We asked what other pathways are regulated by PRDM16 in adipocytes that may be critical for brown and/or beige adipogenesis. Using microarray, we found PRDM16 also represses type I Interferon-stimulated genes (ISGs) in adipocytes.
PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ebf2 is a selective marker of brown and beige adipogenic precursor cells.
Specimen part
View SamplesBrown adipocytes, muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to Pdgfr+, Myf5Cre-lineage-marked cells. RNAseq analysis identified Early B Cell Factor-2 (Ebf2) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2-expressing cells purified from Ebf2-GFP embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2-expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2-expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells.
Ebf2 is a selective marker of brown and beige adipogenic precursor cells.
Specimen part
View SamplesBrown adipocytes, muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to Pdgfra+, Myf5Cre-lineage-marked cells. RNAseq analysis identified Early B Cell Factor-2 (Ebf2) as one of the most selectively expressed genes in this cell fraction. Importantly, Ebf2-expressing cells purified from Ebf2-GFP embryos or brown fat tissue did not express myoblast or dermal cell markers and uniformly differentiated into brown adipocytes. Interestingly, Ebf2-expressing cells from white fat tissue in adult animals differentiated into brown-like (or beige) adipocytes. Loss of Ebf2 in brown preadipose cells reduced the expression levels of brown preadipose-signature genes, whereas ectopic Ebf2-expression in myoblasts activated brown preadipose-specific genes. Altogether, these results indicate that Ebf2 specifically marks and regulates the molecular profile of brown preadipose cells. Overall design: Embryonic fibroblasts, isolated from dorsal body wall of E14.5 Myf5-CrE;mTmG embryos, were further fractionated based on the expression of PDGFRa, Itga7 and Myf5-cre (GFP). Total mRNA profiles from Myf5-cre(GFP)+PDGFRa+ and Myf5-cre(GFP)+PDGFRa-Itga7+ cells were generated by deep sequenceing
Ebf2 is a selective marker of brown and beige adipogenic precursor cells.
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View SamplesIn this dataset, we report the gene expression of adjacent Gleason 3 and Gleason 4 foci microdissected from the same prostate cancer sample.
Gleason Score 7 Prostate Cancers Emerge through Branched Evolution of Clonal Gleason Pattern 3 and 4.
No sample metadata fields
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