Hypoxia transcriptomic time-series data in three different cancer cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE29641 | GEO | 2012/03/01
SECONDARY ACCESSION(S): PRJNA141219
REPOSITORIES: GEO
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Project description:Tumour hypoxia exhibits a highly dynamic spatial and temporal distribution and is associated with increased malignancy and poor prognosis. Assessment of time-dependent gene-expression changes in response to hypoxia may thus provide additional biological insights and help with patient prognosis.
2012-10-12 | GSE41491 | GEO
Project description:Tumour hypoxia exhibits a highly dynamic spatial and temporal distribution and is associated with increased malignancy and poor prognosis. Assessment of time-dependent gene-expression changes in response to hypoxia may thus provide additional biological insights and help with patient prognosis. Transcriptome profiling was performed for 3 cell lines derived from diverse tumour-types after hypoxic exposure at 8 time-points.
2012-10-12 | E-GEOD-41491 | biostudies-arrayexpress
Project description:A hallmark of solid tumours is the development of hypoxic regions where rapidly growing transformed cells outstrip their blood supply. Tumour cells in these starved regions sense reduced levels of oxygen and switch on genes that help them to adapt, survive and continue growing. Since hypoxia is a key physiological difference between normal and cancer tissue, an opportunity exists to selectively kill tumour cells by exploiting the differences in protein expression between normal and hypoxic tumour tissue. However, a major challenge is to identify druggable hypoxia-induced proteins critical for tumour cell survival. This is especially important in cancers of unmet need where hypoxia gene signatures correlate with poor prognosis (for example, colorectal cancers). To identify new hypoxia-induced proteins, we performed SILAC-based proteomics on colorectal cancer cells exposed to normoxia and hypoxia. In this study, we identify a new hypoxia-activated GPCR signalling axis that enables colorectal tumour cells to survive the microenvironmental stress of hypoxia. Our findings uncover a previously unappreciated role for this GPCR-axis as a key regulator of the adaptive response to hypoxia and highlght an opportunity to exploit tumour-associated hypoxia for therapy.
2018-09-18 | PXD009971 | Pride
Project description:Several studies have shown that tumour hypoxia may have a negative impact on the outcome of anticancer treatment. Assessment of tumor hypoxia at baseline or shortly after start of treatment may serve as a predictive marker to determine treatment efficacy at an early stage. Preferably, such an assessment is performed in vivo and non-invasively.Non-invasive imaging with positron emission tomography (PET) using the 2-nitroimidazole nucleoside analogue, 3-18F-fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1- yl)propan-1-ol (18F-HX4), was tested as a new marker of tumor hypoxia. Before hypoxia-measurements can be clinically implemented for response prediction, the reproducibility of the technique should be assessed for each specific tumor type. Knowledge of reproducibility is needed to determine what change in parameters between two examinations can be considered relevant in an individual patient. Assessment of reproducibility becomes even more important in early response monitoring since the changes in the tumor induced by the treatment may be smaller during the treatment compared to response monitoring after completion of treatment. Also, as image quality of 18F-HX4-PET increases with increasing time intervals after injection, determination of the optimal time point for measurement of hypoxia is warranted.
| 2155629 | ecrin-mdr-crc
Project description:General activation of hypoxia-inducible factor (HIF) pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC) HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumour suppressor. However HIF-1a and HIF-2a have contrasting effects on experimental tumour progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1a and HIF-2a and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1a-specific binding, and genes associated with favourable prognosis and between HIF-2a-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-a isoform contributes a highly complex mix of pro- and anti-tumorigenic effects ChIP and RNASeq of HIF-1a and HIF-2a transfection in 786-O cell lines
2015-07-10 | E-GEOD-67237 | biostudies-arrayexpress
Project description:Hypoxia, a hallmark of most solid tumors, leads to aberrations in epigenetic modifications promoting malignant tumor phenotypes, including metastatic features and stem cell-like characteristics. Aberrant DNA methylation has been considered to play an essential role during tumor progression and tightly associate with tumor malignancy. However, the mechanism by which hypoxia alters DNA methylation to promote tumor malignancy remains poorly understood. Ten-eleven translocation 1-3 (TET1-3) proteins, which catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), play a critical role in the DNA demethylation that controls different biological processes. Here we demonstrate that the expression of TET1 and TET3 is closely associated with tumor hypoxia, tumor malignancy and poor prognosis of patients with breast cancer. Hypoxia results in deregulation of TET1 and TET3, leading to breast tumor initiating cell (BTIC) properties. Mechanically, hypoxia regulates expression of TET1 and TET3 via hypoxia-inducible factor-1a (HIF-1a), thereby resulting in 5hmC genome-wide changes, which in turn leads to the upregulation of TNFa expression and activation of its downstream p38-MAPK pathway. Importantly, signal transduction through the TET-TNFa-p38-MAPK signaling axis is required for the acquisition of BTIC characteristics and chemotherapy resistance, leading to more malignant tumor phenotypes. Inhibition of the hypoxia-TET-TNFα-p38-MAPK signaling pathway results in compromised BTIC properties and tumorigenicity in vitro and in vivo, suggesting a possible therapeutic strategy.
2015-10-05 | GSE60434 | GEO
Project description:General activation of hypoxia-inducible factor (HIF) pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC) HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumour suppressor. However HIF-1a and HIF-2a have contrasting effects on experimental tumour progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1a and HIF-2a and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1a-specific binding, and genes associated with favourable prognosis and between HIF-2a-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-a isoform contributes a highly complex mix of pro- and anti-tumorigenic effects
2015-07-10 | GSE67237 | GEO
Project description:Background: Chaperon-mediated autophagy (CMA) has taken on a new emphasis in cancer biology. However, the roles of CMA in hypoxic tumours are poorly understood. We investigated the anti-tumour effects of the natural product ManA through the activation of CMA in tumour progression under hypoxia. Methods: The effect of ManA on CMA activation was assessed in mouse xenograft models and cells. The gene expressions of HIF-1α, HSP90AA1, and transcription factor EB (TFEB) were analysed using The Cancer Genome Atlas (TCGA) datasets to assess the clinical relevance of CMA. Results: ManA activates photoswitchable CMA reporter activity and inhibits Hsp90 chaperone function by disrupting the Hsp90/F1F0-ATP synthase complex. Hsp90 inhibition enhances the interaction between CMA substrates and LAMP-2A and TFEB nuclear localisation, suggesting CMA activation by ManA. ManA-activated CMA retards tumour growth and displays cooperative anti-tumour activity with anti-PD-1 antibody. TCGA datasets show that a combined expression of HSP90AA1High/HIF1AHigh or TFEBLow/HIF1AHigh is strongly correlated with poor prognosis in patients with lung cancer. Conclusions: ManA-induced CMA activation by modulating Hsp90 under hypoxia induces HIF-1α degradation and reduces tumour growth. Thus, inducing CMA activity by targeting Hsp90 may be a promising therapeutic strategy against hypoxic tumours.
2024-01-22 | GSE110768 | GEO
Project description:Multiple myeloma (MM) is the second most common hematologic malignancy, which is characterized by clonal proliferation of neoplastic plasma cells in the bone marrow. This microenvironment is characterized by low oxygen levels (1-6% O2), known as hypoxia. For MM cells, hypoxia is a physiologic feature that has been described to promote an aggressive phenotype and to confer drug resistance. However, studies on hypoxia are scarce and show little conformity. Here, we analyzed the global proteome in MM cells and the stromal cell line HS-5 to reveal hypoxia-dependent regulation of proteins.
2022-02-16 | PXD030239 | Pride
Project description:Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8 T cell responses mediate disease. While these responses originate in the lymph node, we found that expression of the cytolytic effector molecule granzyme B was restricted to lesional CD8 T cells in Leishmania-infected mice, suggesting that local cues within inflamed skin induced cytolytic function. Expression of Blimp-1 (Prdm1), a transcription factor necessary for cytolytic CD8 T cell differentiation, was driven by hypoxia within the inflamed skin. Hypoxia was further enhanced by the recruitment of neutrophils that consumed oxygen to produce reactive oxygen species and ultimately increased the hypoxic state and granzyme B expression in CD8 T cells. Importantly, lesions from cutaneous leishmaniasis patients exhibited hypoxia transcription signatures that correlated with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8 T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as other inflammatory skin diseases where cytolytic CD8 T cells contribute to pathogenesis.
2024-04-29 | GSE193005 | GEO