SUN (Sad1 and UNC-84) and KASH (Klarsicht, ANC-1 and Syne homology) proteins are constituents of the inner and outer nuclear membranes. They interact in the perinuclear space via carboxy-terminal SUN-KASH domains to form the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex thereby bridging the nuclear envelope. LINC complexes sustain numerous biological processes by connecting chromatin with the cytoplasmic force generating machinery. Here we show that the coiled-coil domains of SUN-1 are required for oligomerization and retention of the protein in the nuclear envelope, especially at later stages of female gametogenesis. Consistently, deletion of the coiled coil domain makes SUN-1 sensitive to unilateral force generation across the nuclear membrane. However, absence of this domain does not lead to different expression levels of sun-1 and other known meiotic genes in the mutant compared to wild type. Premature loss of SUN-1 from the nuclear envelope leads to embryonic death due to loss of centrosome-nuclear envelope attachment. However, in contrast to previous notions we can show that the coiled-coil domain is dispensable for functional LINC complex formation, exemplified by successful chromosome sorting and synapsis in meiotic prophase I in their absence. Overall design: A total number five samples were analyzed including two independent wild-type replicates and three independent mutant replicates by PE 50bp RNASeq.
Nuclear Envelope Retention of LINC Complexes Is Promoted by SUN-1 Oligomerization in the Caenorhabditis elegans Germ Line.
Specimen part, Subject
View SamplesTC71 cells treated either with BEZ235 or DMSO
hnRNPM guides an alternative splicing program in response to inhibition of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells.
No sample metadata fields
View SamplesThe thymus constitutes the primary lymphoid organ for the majority of T cells. The phosphatidyl-inositol 3 kinase (PI3K) signaling pathway is involved in lymphoid development. Defects in single components of this pathway prevent thymocytes from progressing beyond early T cell developmental stages. Protein kinase B (PKB) is the main effector of the PI3K pathway. To determine whether PKB mediates PI3K signaling in early T cell development, we characterized PKB knockout thymi. Our results reveal a significant thymic hypocellularity in PKBalpha-/- neonates and an accumulation of early thymocyte subsets in PKBalpha-/- adult mice. The latter finding is specifically attributed to the lack of PKBalpha within the lymphoid component of the thymus. Microarray analyses show that the absence of PKBalpha in early thymocyte subsets modifies the expression of genes known to be involved in pre-TCR signaling, in T cell activation, and in the transduction of interferon-mediated signals. This report highlights the specific requirements of PKBalpha for thymic development.
Deletion of PKBalpha/Akt1 affects thymic development.
Sex, Age, Specimen part
View Samples1. To identify potential effectors responsible for anti-tumorigenesis by targeting PLD1, we performed microarray in two Wnt-relevant colon cancer cells and analyzed transcriptional profile of genes that were differently expressed by inhibition and knockdown of PLD1
Targeting phospholipase D1 attenuates intestinal tumorigenesis by controlling β-catenin signaling in cancer-initiating cells.
Specimen part, Cell line
View SamplesIn vitro experiment of stimulation of monocyte-derived dendritic cells with Saccaromyces cerevisiae in exponential growth phase. This experiment was performed to verify the comparability of microarray
Using pathway signatures as means of identifying similarities among microarray experiments.
No sample metadata fields
View SamplesBRCA1 nestin CRE conditional knockout cortrices of P7 animals were compared to wildtype littermates to characterize the mutant phenotype.
BRCA1 tumour suppression occurs via heterochromatin-mediated silencing.
No sample metadata fields
View SamplesThe combination of JQ1 and Vemurafenib acted synergistically in BRAF-mutant cell lines, resulting in marked apoptosis in vitro, with up-regulation of pro-apoptotic proteins. In vivo, combination treatment suppressed tumor growth and significantly improved survival compared to either drug alone. RNA sequencing of tumor tissues revealed almost four thousand genes that were uniquely modulated by the combination, with several anti-apoptotic genes significantly down-regulated. Overall design: 16 samples analyzed from 8 mice (each mouse was bearing two tumors, one on each flank) in 4 treatment groups (control, vemurafenib alone, JQ1 alone, JQ1+vemurafenib)
BET and BRAF inhibitors act synergistically against BRAF-mutant melanoma.
Cell line, Treatment, Subject
View SamplesPulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy.
Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression.
No sample metadata fields
View SamplesPulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy.
Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression.
Specimen part, Disease, Disease stage, Cell line
View SamplesPulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy.
Canine tumor cross-species genomics uncovers targets linked to osteosarcoma progression.
Specimen part, Disease, Disease stage
View Samples