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hypoxic transcription factor

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https://www.readbyqxmd.com/read/29330809/analysis-of-hypoxia-and-the-hypoxic-response-in-tumor-xenografts
#1
Nuray Böğürcü, Sascha Seidel, Boyan K Garvalov, Till Acker
Solid tumors are often characterized by insufficient oxygen supply (hypoxia), as a result of inadequate vascularization, which cannot keep up with the rapid growth rate of the tumor. Tumor hypoxia is a negative prognostic and predictive factor and is associated with a more aggressive phenotype in various tumor entities. Activation of the hypoxic response in tumors, which is centered around the hypoxia-inducible transcription factors (HIFs), has been causally linked to neovascularization, increased radio- and chemoresistance, altered cell metabolism, genomic instability, increased metastatic potential, and tumor stem cell characteristics...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330807/evaluation-of-macrophage-polarization-in-pancreatic-cancer-microenvironment-under-hypoxia
#2
Kuldeep S Attri, Kamiya Mehla, Pankaj K Singh
Hypoxic microenvironment found in pancreatic ductal adenocarcinoma and other solid tumors is central to physiological and metabolic alterations of immune cells that significantly impact tumor growth dynamics. Hypoxic adaptations in the immune cells are primarily mediated by the stabilization of hypoxia-inducible factor-1 alpha (HIF-1α), which regulates cellular metabolism by modulating glycolysis and other interconnected metabolic pathways. HIF-1α plays distinct roles in M1 and M2 macrophage polarization, which, in turn, regulates tumor cell immune escape and growth...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330794/hypoxia-mediated-in-vivo-tumor-glucose-uptake-measurement-and-analysis
#3
Surendra K Shukla, Scott E Mulder, Pankaj K Singh
Most solid tumors are hypoxic in nature due to the limited supply of oxygen to internal tissues. Hypoxia plays an important role in metabolic adaptations of tumors that contribute significantly to cancer pathogenesis. Among the several metabolic alterations induced by hypoxia, hypoxia-mediated increased glucose uptake serves as the hallmark of metabolic reprogramming. Hypoxia-mediated stabilization of hypoxia-inducible factor-1 alpha (HIF-1α) transcription factor leads to altered expression of several glycolytic genes and glucose transporters, which results in increased glucose uptake by tumor cells...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330790/transcriptional-profiling-using-rna-seq-to-study-hypoxia-mediated-gene-regulation
#4
Surendra K Shukla, Ryan J King, Pankaj K Singh
Exposing cells to a hypoxic environment leads to significant physiological and molecular alterations. Most of the hypoxic responses are regulated by the transcription factors known as hypoxia-inducible factors (HIFs). HIF1, a heterodimer of hypoxia-stabilized subunit HIF-1alpha and a constitutively expressed subunit HIF-1beta, serves as a key transcription factor that regulates gene expressions which are involved in cell growth, metabolism, and proliferation. The global expression patterns can be analyzed by utilizing RNA-Seq to understand the cellular alterations in hypoxia...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29312568/transcriptional-response-to-hypoxic-stress-in-melanoma-and-prognostic-potential-of-gbe1-and-bnip3
#5
Stéphanie Buart, Stéphane Terry, Muhammad Z Noman, Emilie Lanoy, Céline Boutros, Paul Fogel, Philippe Dessen, Guillaume Meurice, Yann Gaston-Mathé, Philippe Vielh, Séverine Roy, Emilie Routier, Virginie Marty, Sophie Ferlicot, Luc Legrès, Morad El Bouchtaoui, Nyam Kamsu-Kom, Jane Muret, Eric Deutsch, Alexander Eggermont, Jean-Charles Soria, Caroline Robert, Salem Chouaib
Gradients of hypoxia occur in most solid tumors and cells found in hypoxic regions are associated with the most aggressive and therapy-resistant fractions of the tumor. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia in melanoma. Using microarray technology, whole genome gene expression profiling was first performed on established melanoma cell lines. From gene set enrichment analyses, we derived a robust 35 probes signature (hypomel for HYPOxia MELanoma) associated with hypoxia-response pathways, including 26 genes up regulated, and 9 genes down regulated...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29306548/disrupting-the-warburg-effect-re-routes-cancer-cells-to-oxphos-offering-a-vulnerability-point-via-ferroptosis-induced-cell-death
#6
REVIEW
Maša Ždralević, Milica Vučetić, Boutaina Daher, Ibtissam Marchiq, Scott K Parks, Jacques Pouysségur
The evolution of life from extreme hypoxic environments to an oxygen-rich atmosphere has progressively selected for successful metabolic, enzymatic and bioenergetic networks through which a myriad of organisms survive the most extreme environmental conditions. From the two lethal environments anoxia/high O2, cells have developed survival strategies through expression of the transcriptional factors ATF4, HIF1 and NRF2. Cancer cells largely exploit these factors to thrive and resist therapies. In this review, we report and discuss the potential therapeutic benefit of disrupting the major Myc/Hypoxia-induced metabolic pathway, also known as fermentative glycolysis or "Warburg effect", in aggressive cancer cell lines...
December 28, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29299120/hif-1%C3%AE-contributes-to-hypoxia-adaptation-of-the-naked-mole-rat
#7
Bang Xiao, Shiyong Wang, Guoshi Yang, Xiaoxi Sun, Shanmin Zhao, Lifang Lin, Jishuai Cheng, Wenjing Yang, Wei Cong, Wei Sun, Guanghan Kan, Shufang Cui
Background/Aims: Naked mole rats (NMRs) spend their lives in burrow systems containing very low levels of oxygen, indicating long-term hypoxic exposure, and suggesting that pathological changes caused by hypoxia are attenuated or absent in this hypoxia-tolerant species. The mechanisms underlying NMRs hypoxia tolerance remain poorly understood. In this study, we explored whether hypoxia inducible factor 1α (HIF-1α), and vascular endothelial growth factor A (VEGFA) play a role in NMRs adaption to hypoxia...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285165/mitokatp-channels-promote-the-proliferation-of-hypoxic-human-pulmonary-artery-smooth-muscle-cells-via-the-ros-hif-mir-210-iscu-signaling-pathway
#8
Hongling Hu, Yu Ding, Yang Wang, Shuang Geng, Jue Liu, Jinrong He, Yang Lu, Xueying Li, Mingli Yuan, Shan Zhu, Su Zhao
Previous results have indicated that mitochondrial ATP-sensitive potassium (mitoKATP) channels are associated with the hypoxic proliferation of pulmonary artery smooth muscle cells (PASMCs). However, the mechanism underlying the promotive effects of mitoKATP channels on cell proliferation in response to hypoxia remains unknown. mitoKATP channel opening results in a collapse of mitochondrial membrane potential and generation of mitochondrial reactive oxygen species (ROS). As hypoxia-inducible factor-1α (HIF-1α) is a critical oxygen sensor and major transcriptional regulator of the hypoxic adaptive response, the current study assessed whether mitoKATP opening contributes to the chronic proliferation of human PASMCs (hPASMCs) in collaboration with HIF-1α and its downstream targets under hypoxic conditions...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29277613/hypoxia-induced-activation-of-twist-mir-214-e-cadherin-axis-promotes-renal-tubular-epithelial-cell-mesenchymal-transition-and-renal-fibrosis
#9
Minna Liu, Limin Liu, Ming Bai, Lei Zhang, Feng Ma, Xiaoxia Yang, Shiren Sun
The epithelial-to-mesenchymal transition (EMT) induced by chronic hypoxia is one of the critical causes of renal fibrosis. Previous work reported that the transcription factors Twist plays an important role in hypoxia-induced EMT and renal fibrosis. Recent evidence indicates that miR-214 was regulated by Twist in many fibrotic diseases, but their role in hypoxia-induced EMT and renal fibrosis remains unknown. Here, we found that hypoxia significantly upregulated the expression of miR-214-3p in HK-2 cells, unilateral ureteral obstruction (UUO) nephropathy and patients with chronic kidney disease...
December 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29246927/disruption-of-interneuron-neurogenesis-in-premature-newborns-and-reversal-with-estrogen-treatment
#10
Mahima Tibrewal, Bokun Cheng, Preeti Dohare, Furong Hu, Rana Mehdizadeh, Ping Wang, Deyou Zheng, Zoltan Ungvari, Praveen Ballabh
Preterm-born children suffer from neurobehavioral disorders. Premature birth terminates the hypoxic in utero environment and supply of maternal hormones. As the production of interneurons continues until the end of pregnancy, we hypothesized that premature birth would disrupt interneuron production and restoration of the hypoxic milieu or estrogen treatment might reverse interneuron generation. To test these hypotheses, we quantified interneuronal progenitors in the medial, lateral, and caudal ganglionic eminences (MGE, LGE, and CGE) of preterm- (E29 at D3 and D7) vs...
December 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29246704/the-effect-of-within-instar-development-on-tracheal-diameter-and-hypoxia-inducible-factors-%C3%AE-and-%C3%AE-in-the-tobacco-hornworm-manduca-sexta
#11
Taylor Lundquist, Jeffrey Kittilson, Rubina Ahsan, Kendra Greenlee
As insects grow within an instar, body mass increases, often more than doubling. The increase in mass causes an increase in metabolic rate and hence oxygen demand. However, the insect tracheal system is hypothesized to increase only after molting and may be compressed as tissues grow within an instar. The increase in oxygen demand in the face of a potentially fixed or decreasing supply could result in hypoxia as insects near the end of an instar. To test these hypotheses, we first used synchrotron x-ray imaging to determine how diameters of large tracheae change within an instar and after molting to the next instar in the tobacco hornworm, Manduca sexta...
December 12, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/29226333/p53-and-mir-210-regulated-neurod2-a-neuronal-basic-helix-loop-helix-transcription-factor-is-downregulated-in-glioblastoma-patients-and-functions-as-a-tumor-suppressor-under-hypoxic-microenvironment
#12
Rahul Agrawal, Ankita Garg, Prit Benny Malgulwar, Vikas Sharma, Chitra Sarkar, Ritu Kulshreshtha
The factors involved in cell differentiation have recently garnered interest for their role in inhibition of pathogenesis in various tumors. However, their role in glioblastoma (GBM) remains poorly understood. We analyzed the TCGA-GBM data and found significant downregulation of neurogenic differentiation factor NeuroD2 in GBM patients. Low levels of NeuroD2 were found to be correlated with poor overall survival of GBM patients in TCGA dataset as well as in our cohort. Interestingly, NeuroD2 was shown to be transcriptionally induced by p53 and post-transcriptionally targeted by hypoxia inducible miRNA, miR-210...
December 11, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29212519/gper-mediates-the-angiocrine-actions-induced-by-igf1-through-the-hif-1%C3%AE-vegf-pathway-in-the-breast-tumor-microenvironment
#13
Ernestina M De Francesco, Andrew H Sims, Marcello Maggiolini, Federica Sotgia, Michael P Lisanti, Robert B Clarke
BACKGROUND: The G protein estrogen receptor GPER/GPR30 mediates estrogen action in breast cancer cells as well as in breast cancer-associated fibroblasts (CAFs), which are key components of microenvironment driving tumor progression. GPER is a transcriptional target of hypoxia inducible factor 1 alpha (HIF-1α) and activates VEGF expression and angiogenesis in hypoxic breast tumor microenvironment. Furthermore, IGF1/IGF1R signaling, which has angiogenic effects, has been shown to activate GPER in breast cancer cells...
December 6, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/29205072/enamel-matrix-proteins-regulate-hypoxia-induced-cellular-biobehavior-and-osteogenic-differentiation-in-human-periodontal-ligament-cells
#14
Z C Song, S Li, J C Dong, M J Sun, X L Zhang, R Shu
Hypoxia is a crucial microenvironment for inflamed periodontal tissue and periodontal wound healing. Enamel matrix proteins (EMPs) potentially can promote the formation of new periodontium. The effects of EMPs on periodontal ligament cells under hypoxia, however, remain unclear. We investigated the effects of EMPs on cellular biobehavior and osteogenic differentiation of human periodontal ligament cells (hPDLCs) under hypoxia. Under cobalt chloride (CoCl2)-induced hypoxia, cellular biobehavior of hPDLCs, including proliferation, attachment, spreading, and migration with or without EMPs, was evaluated by 3-(4, 5-dimethylthiazol- 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT), cell counting, spreading area measurement and wound scratch assay...
December 5, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/29185141/tip-cell-behavior-is-regulated-by-transcription-factor-foxo1-under-hypoxic-conditions-in-developing-mouse-retinas
#15
Moe Fukumoto, Kanako Kondo, Kazumasa Uni, Tomoko Ishiguro, Mikiko Hayashi, Shinnosuke Ueda, Itsuki Mori, Kenta Niimi, Fumi Tashiro, Satsuki Miyazaki, Jun-Ichi Miyazaki, Shinobu Inagaki, Tatsuo Furuyama
Forkhead box protein O1 (FoxO1) is a transcription factor and a critical regulator of angiogenesis. Various environmental stimuli, including growth factors, nutrients, shear stress, oxidative stress and hypoxia, affect FoxO1 subcellular localization and strongly influence its transcriptional activity; however, FoxO1-localization patterns in endothelial cells (ECs) during development have not been clarified in vivo. Here, we reported that FoxO1 expression was observed in three layers of angiogenic vessels in developing mouse retinas and that among these layers, the front layer showed high levels of FoxO1 expression in the nuclei of most tip ECs...
November 28, 2017: Angiogenesis
https://www.readbyqxmd.com/read/29155844/hypoxia-and-hypoxia-inducible-factor-hif-downregulate-antigen-presenting-mhc-class-i-molecules-limiting-tumor-cell-recognition-by-t-cells
#16
Shalini Sethumadhavan, Murillo Silva, Phaethon Philbrook, Thao Nguyen, Stephen M Hatfield, Akio Ohta, Michail V Sitkovsky
Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF...
2017: PloS One
https://www.readbyqxmd.com/read/29155422/secretion-mediated-stat3-activation-promotes-self-renewal-of-glioma-stem-like-cells-during-hypoxia
#17
D A Almiron Bonnin, M C Havrda, M C Lee, H Liu, Z Zhang, L N Nguyen, L X Harrington, S Hassanpour, C Cheng, M A Israel
High-grade gliomas (HGGs) include the most common and the most aggressive primary brain tumor of adults and children. Despite multimodality treatment, most high-grade gliomas eventually recur and are ultimately incurable. Several studies suggest that the initiation, progression, and recurrence of gliomas are driven, at least partly, by cancer stem-like cells. A defining characteristic of these cancer stem-like cells is their capacity to self-renew. We have identified a hypoxia-induced pathway that utilizes the Hypoxia Inducible Factor 1α (HIF-1α) transcription factor and the JAK1/2-STAT3 (Janus Kinase 1/2 - Signal Transducer and Activator of Transcription 3) axis to enhance the self-renewal of glioma stem-like cells...
November 20, 2017: Oncogene
https://www.readbyqxmd.com/read/29147618/programmed-cell-death-ligands-expression-in-phaeochromocytomas-and-paragangliomas-relationship-with-the-hypoxic-response-immune-evasion-and-malignant-behavior
#18
David J Pinato, James R Black, Sebastian Trousil, Roberto E Dina, Pritesh Trivedi, Francesco A Mauri, Rohini Sharma
The hypoxic response underlies the pathogenesis and malignant behavior of PCC/PGL. Regulation of PD-1 receptor-ligand signaling, a therapeutically actionable driver of the anti-tumor immune response, is a hypoxic-driven trait across malignancies. We evaluated the prognostic role of PD ligands in association with biomarkers of hypoxia and angiogenesis in patients with PCC/PGL. Tissue microarrays sections including consecutive cases diagnosed between 1983-2011 were stained for PD-L1 and 2, hypoxia inducible factor 1a (Hif-1a), Carbonic Anhydrase IX (CaIX), Vascular Endothelial Growth Factor-A (VEGF-A)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29145444/inhibition-of-the-h3k9-methyltransferase-g9a-attenuates-oncogenicity-and-activates-the-hypoxia-signaling-pathway
#19
Jolene Caifeng Ho, Lissa Nurrul Abdullah, Qing You Pang, Sudhakar Jha, Edward Kai-Hua Chow, Henry Yang, Hiroyuki Kato, Lorenz Poellinger, Jun Ueda, Kian Leong Lee
Epigenetic mechanisms play important roles in the regulation of tumorigenesis, and hypoxia-induced epigenetic changes may be critical for the adaptation of cancer cells to the hypoxic microenvironment of solid tumors. Previously, we showed that loss-of-function of the hypoxia-regulated H3K9 methyltransferase G9A attenuates tumor growth. However, the mechanisms by which blockade of G9A leads to a tumor suppressive effect remain poorly understood. We show that G9A is highly expressed in breast cancer and is associated with poor patient prognosis, where it may function as a potent oncogenic driver...
2017: PloS One
https://www.readbyqxmd.com/read/29136509/an-hif-1%C3%AE-vegf-a-axis-in-cytotoxic-t-cells-regulates-tumor-progression
#20
Asis Palazon, Petros A Tyrakis, David Macias, Pedro Veliça, Helene Rundqvist, Susan Fitzpatrick, Nikola Vojnovic, Anthony T Phan, Niklas Loman, Ingrid Hedenfalk, Thomas Hatschek, John Lövrot, Theodoros Foukakis, Ananda W Goldrath, Jonas Bergh, Randall S Johnson
Cytotoxic T cells infiltrating tumors are thought to utilize HIF transcription factors during adaptation to the hypoxic tumor microenvironment. Deletion analyses of the two key HIF isoforms found that HIF-1α, but not HIF-2α, was essential for the effector state in CD8+ T cells. Furthermore, loss of HIF-1α in CD8+ T cells reduced tumor infiltration and tumor cell killing, and altered tumor vascularization. Deletion of VEGF-A, an HIF target gene, in CD8+ T cells accelerated tumorigenesis while also altering vascularization...
November 13, 2017: Cancer Cell
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