Inhibiting the unfolded protein response (UPR) can be a therapeutic approach, especially for targeting the tumor microenvironment. We found that compound C (also known as dorsomorphin) prevented the UPR and exerted enhanced cytotoxicity during glucose deprivation. The UPR-inhibiting activity of compound C was not associated with either AMPK or BMP signaling inhibition.
Compound C prevents the unfolded protein response during glucose deprivation through a mechanism independent of AMPK and BMP signaling.
Specimen part, Cell line
View SamplesCancer cells consume large amounts of glucose because of their specific metabolic pathway. However, cancer cells exist in tumor tissue where glucose is insufficient. To survive, cancer cells likely have the mechanism to elude their glucose addiction. Here we show that functional mitochondria are essential if cancer cells are to avoid glucose addiction.
Mitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions.
Disease, Cell line, Time
View SamplesThe unfolded protein response (UPR) is a cellular defense mechanism against glucose deprivation, a cell condition that occurs in solid tumors.
Chemical genomics identifies the unfolded protein response as a target for selective cancer cell killing during glucose deprivation.
No sample metadata fields
View SamplesMitochondria can be involved in regulating cellular stress response to hypoxia and tumor growth, but little is known about that mechanistic relationship. Here, we show that mitochondrial deficiency severely retards tumor xenograft growth with impairing hypoxic induction of HIF-1 transcriptional activity. Using mtDNA-deficient rho0 cells, we found that HIF-1 pathway activation was comparable in slow-growing rho0 xenografts and rapid-growing parental xenografts. Interestingly, we found that ex vivo rho0 cells derived from rho0 xenografts exhibited slightly increased HIF-1alpha expression and modest HIF-1 pathway activation regardless of oxygen concentration. Surprisingly, rho0 cells, as well as parental cells treated with oxidative phosphorylation inhibitors, were unable to boost HIF-1 transcriptional activity during hypoxia, although HIF-1alpha protein levels were ordinarily increased in these cells under hypoxic conditions. These findings indicate that mitochondrial deficiency causes loss of hypoxia-induced HIF-1 transcriptional activity and thereby might lead to a constitutive HIF-1 pathway activation as a cellular adaptation mechanism in tumor microenvironment.
Mitochondrial deficiency impairs hypoxic induction of HIF-1 transcriptional activity and retards tumor growth.
Cell line
View SamplesRNA-Seq analysis of SSA treated cells Overall design: HeLa cells, nuclear and cytoplasmic fractions, treated with SSA or MeOH
Global analysis of pre-mRNA subcellular localization following splicing inhibition by spliceostatin A.
No sample metadata fields
View SamplesHMGN1 contributes to the shortened latency of liver tumorigenesis by changing a chromatin structure and expression of relevant genes
Loss of the nucleosome-binding protein HMGN1 affects the rate of N-nitrosodiethylamine-induced hepatocarcinogenesis in mice.
Specimen part, Treatment
View SamplesHyperthermia is widely used to treat patients with various cancers. The 42.5C is well known as inflection point of hyperthermia and generally up to 42C of hyperthermia is used in clinical case to combine with other therapy. Here, the effects of heat stress at 42 or 44C for 90 min on the gene expression in HSC-3 human oral squamous carcinoma cells were investigated using an Affymetrix GeneChip system. The cells were treated with heat stress (42 or 44C for 90 min) and followed by incubation for 0, 6, or 12 h at 37C. The percentage of cell death was 5.0 1.5 (mean SD) at 42C for 12 h and 17.4 0.6 at 44C for 12 h. Of approximately 47,000 probe sets analyzed, many genes that were differentially expressed by a factor 2.0 or greater were identified in the cells treated with heat stress at 42 and 44C.
Gene networks related to the cell death elicited by hyperthermia in human oral squamous cell carcinoma HSC-3 cells.
Cell line, Treatment, Time
View SamplesL-Ser deficiency leads to growth arrest, tissue malformation and embryonic lethality in mice. However, the molecular mechanism by which L-Ser deficiency impairs basic cellular function remains largely unexplored.
Microarray data on altered transcriptional program of Phgdh-deficient mouse embryonic fibroblasts caused by ʟ-serine depletion.
Specimen part
View SamplesPiwi proteins and Piwi-interacting small RNAs (piRNAs) have known functions in transposon silencing in the male germline of fetal and newborn mice. Both are also necessary for spermatogenesis in adult testes, however, their function here remains a mystery. Here, we use germ cell isolations and small RNA sequencing to show that most piRNAs in meiotic spermatocytes originate from clusters in intergenic non-repeat regions of DNA. The regulation of these piRNA clusters, including the processing of the precursor transcripts into individual piRNAs, is accomplished through mostly unknown processes. We present evidence for a regulatory mechanism for one such cluster, named cluster 1082B, located on chromosome 7 in the mouse genome, containing 788 unique piRNAs. The precursor transcript and individual piRNAs within the cluster are repressed by the Alkbh1 dioxygenase and the transcription repressor Tzfp, which are believed to be interaction partners in testis. We observe more than a thousand-fold upregulation of individual piRNAs in pachytene spermatocytes isolated from Alkbh1-/- and TzfpGTi/GTi testes. Repression is further supported by the identification of a 10 bp Tzfp recognition sequence contained within the precursor transcript. Downregulation of long interspersed elements 1 (LINE1) and intracisternal A-particle (IAP) transcripts in the Alkbh1-/- and TzfpGTi/GTi testes leads us to propose a potential role for the 1082B-encoded piRNAs in transposon silencing. Overall design: Characterization of small RNAs in mouse pachytene spermatocytes for wild-type (WT) and Alkbh1-/- and TzfpGTi/GTi, and mRNA in mouse pachytene spermatocytes for wild-type (WT) and Alkbh1-/-
Alkbh1 and Tzfp repress a non-repeat piRNA cluster in pachytene spermatocytes.
Specimen part, Subject
View SamplesWe established transgenic mice overexpressing the histone demethyase LSD1/KDM1A under the control of Sca-1 promoter and investigated the global changes in gene expression in hematopoietic progenitor cells using a microarray-
Overexpression of the shortest isoform of histone demethylase LSD1 primes hematopoietic stem cells for malignant transformation.
Specimen part
View Samples