Alveolar rhabdomyosarcoma (aRMS) is a soft tissue sarcoma associated with the skeletal muscle lineage. The majority of aRMS tumors express the fusion protein PAX3-FOXO1 (PF), which has proven chemically intractable. As such, we identified proteins downstream from or cooperate with PF to support tumorigenesis, including SFRP3 (FRZB). Suppression of SFRP3 using lentivirally transduced shRNAs inhibits cell growth in vitro and tumor growth in vivo. This study aims to identify the genetic changes that underlie the SFRP3 suppression-mediated decreased cell growth. We analyzed changes using Gene Ontology (GO) enrichment and found the induced genes were enriched in striated muscle development/differentiation. In contrast, the repressed genes were enriched in response to stimulus and cell cycle/mitosis genes. We also observed as expected downregulation of SFRP3 (FRZB) but also downregulation of Wnt pathway-repressing genes such as CTBP2 (a transcriptional repressor of TCF, similar to CTBP1 ) and NAV2 (which is downstream from APC). Conversely, we noted upregulation of genes including CCND1 (cyclin D1) and SNAI2 (SLUG), both Wnt signaling target genes and WNT6, which is known to inhibit myoblast proliferation but induce myoblast elongation.
Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3-FOXO1-Positive Alveolar Rhabdomyosarcoma.
Disease, Cell line, Treatment
View SamplesAlveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle characterized by expression of the PAX3-FOXO1 fusion gene. Despite its discovery over almost 20 years ago, PAX3-FOXO1 remains an enigmatic tumor driver. Previously, we reported that PAX3-FOXO1 supports aRMS initiation by enabling bypass of cellular senescence. Here, we show that bypass occurs in part by PAX3-FOXO1-mediated upregulation of RASSF4, a Ras-association domain family (RASSF) member, which then suppresses the evolutionarily conserved mammalian Hippo/Mst1 pathway. RASSF4 loss-of-function activates Hippo/Mst1 and inhibits downstream YAP, causing aRMS cell cycle arrest and senescence. This is the first evidence for an oncogenic role for RASSF4, and a novel mechanism for Hippo signaling suppression in human cancer.
Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression.
Cell line, Treatment
View SamplesWe used microarrays to detail gene expression changes in Hs 294T human melanoma cells after treatment with elesclomol alone, or in combination with paclitaxel, to aide in identifing the mechnism of action of elesclomol.
Elesclomol induces cancer cell apoptosis through oxidative stress.
No sample metadata fields
View SamplesWe used microarrays to detail gene expression changes in Hs 294T human melanoma cells after treatment with elesclomol alone, or in combination with NAC, to aide in identifing the mechnism of action of elesclomol.
Elesclomol induces cancer cell apoptosis through oxidative stress.
No sample metadata fields
View SamplesFoxp1 is expressed throughout B cell development, but the physiological functions in mature B lymphocytes are unknown. We therefore evaluated differential gene expression in Foxp1-deficient B cells, with or
Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells.
Specimen part
View SamplesWe used a RAG2-GFP reporter mouse to show that RAG+ B lineage cells can be found in the small intestinal lamina proria in normally-housed mice at weaning age. We used microarry expression analysis to compare the RAG2+ population in the gut to the RAG2+ B lineage population in the bone marrow.
Microbial colonization influences early B-lineage development in the gut lamina propria.
Specimen part
View SamplesT cell lymphoma
PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis.
Sex, Specimen part, Cell line
View SamplesThe acquisition of water and nutrients by plant roots is a fundamental aspect of agriculture and strongly depends on root architecture. Root branching and expansion of the root system is achieved through the development of lateral roots and is to a large extent controlled by the plant hormone auxin. However, the pleiotropic effects of auxin or auxin-like molecules on root systems complicate the study of lateral root development. Here we describe a small-molecule screen in Arabidopsis thaliana that identified naxillin as what is to our knowledge the first non-auxin-like molecule that promotes root branching. By using naxillin as a chemical tool, we identified a new function for root cap-specific conversion of the auxin precursor indole-3-butyric acid into the active auxin indole-3-acetic acid and uncovered the involvement of the root cap in root branching. Delivery of an auxin precursor in peripheral tissues such as the root cap might represent an important mechanism shaping root architecture. To further explore the specificity of naxillin for lateral root development, we compared the early effects of naxillin at the transcriptome level with NAA (1-Naphthaleneacetic acid) in roots of 3-day-old seedlings after 2-h and 6-h treatment.
A role for the root cap in root branching revealed by the non-auxin probe naxillin.
Age, Specimen part, Treatment
View SamplesHere we used microarray expression profiling to characterise global changes in gene expression during stages of proliferation and differentiation of human neural stem cells
Associations of the Intellectual Disability Gene MYT1L with Helix-Loop-Helix Gene Expression, Hippocampus Volume and Hippocampus Activation During Memory Retrieval.
Specimen part, Cell line
View Samples