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GSE76675
Homo sapiens
24 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Many cancers rely on glycolytic metabolism to fuel rapid proliferation. This has spurred interest in designing drugs that target tumor glycolysis such as AZD3965, a small molecule inhibitor of Monocarboxylate Transporter 1 (MCT1) currently undergoing Phase I evaluation for cancer treatment. Since MCT1 mediates proton-linked transport of monocarboxylates such as lactate and pyruvate across the plasma membrane (Halestrap and Meredith, 2004), AZD3965 is thought to block tumor growth through disruption of lactate transport and glycolysis. Here we show that MCT1 inhibition impairs proliferation of glycolytic breast cancer cells that express MCT4 via disruption of pyruvate rather than lactate export. We found that MCT1 expression is elevated in glycolytic breast tumors and cell lines as well as in malignant breast and lung tissues. High MCT1 expression predicts poor prognosis in breast and lung cancer patients. Stable knockdown and AZD3965-mediated inhibition of MCT1 promote oxidative metabolism. Acute inhibition of MCT1 reduces pyruvate export rate but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that also express MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest that MCT1 expression is elevated in glycolytic cancers to promote pyruvate export, which when inhibited enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors that further supports their use as anti-cancer therapeutics.
Publication Title
MCT1 Modulates Cancer Cell Pyruvate Export and Growth of Tumors that Co-express MCT1 and MCT4.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mantle cell lymphoma (MCL) is an aggressive neoplasm with poor outcome. However, some patients have an indolent disease (iMCL) and may not require intensive treatment at initial diagnosis. Diagnostic criteria to recognize these patients are not available. We hypothesized that the analysis of the genetic and expression features of the tumors may help to identify patients with an indolent clinical evolution and provide biomarkers that could be used in the clinical setting.
Publication Title
Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma.
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Robles-Valero et al. report a tumor suppression role for the otherwise oncogenic Vav1 Rho GEF. This paradoxical action is mediated by the catalysis-independent buffering of Notch1 signaling in immature T cells.
Publication Title
A Paradoxical Tumor-Suppressor Role for the Rac1 Exchange Factor Vav1 in T Cell Acute Lymphoblastic Leukemia.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
While several physiological skin parameters vary in a circadian manner, the identity of genes participating in chronobiology of skin remains unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle related genes, the former peaking during the day and the latter peaking at the night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes as keratinocyte-specific deletion of Bmal1 obliterates time of day dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. Consistent with higher cellular susceptibility to UV-induced DNA damage during S phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. As maximum numbers of keratinocytes go through S phase in the late afternoon in the human epidermis, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation such that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers.
Publication Title
Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
While several physiological skin parameters vary in a circadian manner, the identity of genes participating in chronobiology of skin remains unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle related genes, the former peaking during the day and the latter peaking at the night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes as keratinocyte-specific deletion of Bmal1 obliterates time of day dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. Consistent with higher cellular susceptibility to UV-induced DNA damage during S phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. As maximum numbers of keratinocytes go through S phase in the late afternoon in the human epidermis, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation such that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers.
Publication Title
Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
While several physiological skin parameters vary in a circadian manner, the identity of genes participating in chronobiology of skin remains unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle related genes, the former peaking during the day and the latter peaking at the night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes as keratinocyte-specific deletion of Bmal1 obliterates time of day dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. Consistent with higher cellular susceptibility to UV-induced DNA damage during S phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. As maximum numbers of keratinocytes go through S phase in the late afternoon in the human epidermis, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation such that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers.
Publication Title
Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The Mediator complex allows communication between transcription factors and RNA polymerase II (RNAPII). CDK8, the kinase found in some variants of Mediator, has been characterized mostly as a transcriptional repressor. Recently, CDK8 was demonstrated to be a potent oncoprotein. Here we show that CDK8 is predominantly a positive regulator of gene expression within the serum response network, as it is required for expression of several members of the AP-1 and EGR family of oncogenic transcription factors (e.g. FOS, JUN, EGR1-3). Mechanistic studies demonstrate that CDK8 is not required for recruitment of RNAPII and promoter escape at these loci. Instead, CDK8 depletion leads to the appearance of slower elongation complexes carrying hypophosphorylated RNAPII. We show that CDK8-Mediator regulates precise steps in the assembly of a functional elongation complex, including the recruitment of P-TEFb and BRD4, but is dispensable for recruitment of SPT5 and FACT. Furthermore, CDK8-Mediator specifically interacts with P-TEFb. Thus, we uncovered a novel role for CDK8 in transcriptional regulation that may contribute to its oncogenic effects.
Publication Title
CDK8 is a positive regulator of transcriptional elongation within the serum response network.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Ibf1 and Ibf2 are novel CP190-interacting proteins required for insulator function.
Sample Metadata Fields
Disease, Cell line
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Gene expression in S2 cells after CG9740 or CP190 RNAi
Publication Title
Ibf1 and Ibf2 are novel CP190-interacting proteins required for insulator function.
Sample Metadata Fields
Cell line
View Samples