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oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-b receptors (TGF-bRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3′-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency-associated transcription factors (Oct-3/4, Nanog and Sox-2), glycolysis-and epithelial-mesenchymal transition (EMT) programme-associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self-renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse.","publication_date":"2013,,","publication_name":"Journal of Cellular and Molecular Medicine","grobid_abstract_attachment_id":"109838598"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [297774849]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = 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ds-top-related-works--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="0" data-entity-id="15334085" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/15334085/HIF_expression_and_the_role_of_hypoxic_microenvironments_within_primary_tumours_as_protective_sites_driving_cancer_stem_cell_renewal_and_metastatic_progression">HIF expression and the role of hypoxic microenvironments within primary tumours as protective sites driving cancer stem cell renewal and metastatic progression</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="34450329" href="https://griffith.academia.edu/StephenRalph">Stephen Ralph</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Carcinogenesis, 2013</p><div 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Critical mediators of the hypoxic response are the hypoxia-inducible factors HIF-1α and HIF-2α. The HIFs are nonredundant and regulate both overlapping and unique downstream target genes. Here, we describe a novel mechanism for the switch between HIF-1α- and HIF-2α–dependent transcription during tumor hypoxia caused by the hypoxia associated factor (HAF). HAF is overexpressed in a variety of tumors and its levels are decreased during acute hypoxia, but increased following prolonged hypoxia. We have previously identified HAF as an E3 ubiquitin ligase that binds and ubiquitinates HIF-1α by an oxygen and pVHL-independent mechanism, thus targeting HIF-1α for proteasomal degradation. Here, we show that HAF also binds to HIF-2α, but at a different site than HIF-1α, and increases HIF-2α transactivation w...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The Hypoxia-Associated Factor Switches Cells from HIF-1α- to HIF-2α-Dependent Signaling Promoting Stem Cell Characteristics, Aggressive Tumor Growth and Invasion","attachmentId":104743300,"attachmentType":"pdf","work_url":"https://www.academia.edu/105232962/The_Hypoxia_Associated_Factor_Switches_Cells_from_HIF_1%CE%B1_to_HIF_2%CE%B1_Dependent_Signaling_Promoting_Stem_Cell_Characteristics_Aggressive_Tumor_Growth_and_Invasion","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/105232962/The_Hypoxia_Associated_Factor_Switches_Cells_from_HIF_1%CE%B1_to_HIF_2%CE%B1_Dependent_Signaling_Promoting_Stem_Cell_Characteristics_Aggressive_Tumor_Growth_and_Invasion"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="121707617" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/121707617/Therapeutic_Targeting_Hypoxia_Inducible_Factor_HIF_1_in_Cancer_Cutting_Gordian_Knot_of_Cancer_Cell_Metabolism">Therapeutic Targeting Hypoxia-Inducible Factor (HIF-1) in Cancer: Cutting Gordian Knot of Cancer Cell Metabolism</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="41271470" href="https://independent.academia.edu/shrivastavaneeta">neeta shrivastava</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Frontiers in Genetics</p><p class="ds-related-work--abstract ds2-5-body-sm">Metabolic alterations are one of the hallmarks of cancer, which has recently gained great attention. Increased glucose absorption and lactate secretion in cancer cells are characterized by the Warburg effect, which is caused by the metabolic changes in the tumor tissue. Cancer cells switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis due to changes in glucose degradation mechanisms, a process known as “metabolic reprogramming”. As a result, proteins involved in mediating the altered metabolic pathways identified in cancer cells pose novel therapeutic targets. Hypoxic tumor microenvironment (HTM) is anticipated to trigger and promote metabolic alterations, oncogene activation, epithelial-mesenchymal transition, and drug resistance, all of which are hallmarks of aggressive cancer behaviour. Angiogenesis, erythropoiesis, glycolysis regulation, glucose transport, acidosis regulators have all been orchestrated through the activation and stability of a transcription facto...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Therapeutic Targeting Hypoxia-Inducible Factor (HIF-1) in Cancer: Cutting Gordian Knot of Cancer Cell Metabolism","attachmentId":116524389,"attachmentType":"pdf","work_url":"https://www.academia.edu/121707617/Therapeutic_Targeting_Hypoxia_Inducible_Factor_HIF_1_in_Cancer_Cutting_Gordian_Knot_of_Cancer_Cell_Metabolism","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/121707617/Therapeutic_Targeting_Hypoxia_Inducible_Factor_HIF_1_in_Cancer_Cutting_Gordian_Knot_of_Cancer_Cell_Metabolism"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="29059573" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/29059573/Hypoxia_inducible_factors_in_cancer_stem_cells">Hypoxia inducible factors in cancer stem cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32839439" href="https://ua-birmingham.academia.edu/AnitaHjelmeland">Anita Hjelmeland</a></div><p class="ds-related-work--metadata ds2-5-body-xs">British journal of cancer, 2010</p><p class="ds-related-work--abstract ds2-5-body-sm">Oxygen is an essential regulator of cellular metabolism, survival, and proliferation. Cellular responses to oxygen levels are monitored, in part, by the transcriptional activity of the hypoxia inducible factors (HIFs). Under hypoxia, HIFs regulate a variety of pro-angiogenic and pro-glycolysis pathways. In solid cancers, regions of hypoxia are commonly present throughout the tissue because of the chaotic vascular architecture and regions of necrosis. In these regions, the hypoxic state fluctuates in a spatial and temporal manner. Transient hypoxic cycling causes an increase in the activity of the HIF proteins above what is typical for non-pathologic tissue. The extent of hypoxia strongly correlates to poor patient survival, therapeutic resistance and an aggressive tumour phenotype, but the full contribution of hypoxia and the HIFs to tumour biology is an area of active investigation. Recent reports link resistance to conventional therapies and the metastatic potential to a stem-like...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia inducible factors in cancer stem cells","attachmentId":49513657,"attachmentType":"pdf","work_url":"https://www.academia.edu/29059573/Hypoxia_inducible_factors_in_cancer_stem_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/29059573/Hypoxia_inducible_factors_in_cancer_stem_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="116201578" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/116201578/Drug_resistance_and_cancer_stem_cells_the_shared_but_distinct_roles_of_hypoxia_inducible_factors_HIF1%CE%B1_and_HIF2%CE%B1">Drug resistance and cancer stem cells: the shared but distinct roles of hypoxia‐inducible factors HIF1α and HIF2α</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="37761808" href="https://independent.academia.edu/GuWenyi">Wenyi Gu</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Clinical and Experimental Pharmacology and Physiology, 2017</p><p class="ds-related-work--abstract ds2-5-body-sm">SummaryChemotherapy resistance is a major contributor to poor treatment responses and tumour relapse, the development of which has been strongly linked to the action of cancer stem cells (CSCs). Mounting evidence suggests that CSCs are reliant on low oxygen conditions and hypoxia‐inducible factors 1α and 2α (HIF1α and HIF2α) to maintain their stem cell features. Research in the last decade has begun to clarify the functional differences between the two HIFα subtypes (HIFαs). Here, we review and discuss these differences in relation to CSC‐associated drug resistance. Both HIFαs contribute to CSC survival but play different roles –HIF1α being more responsible for survival functions and HIF2α for stemness traits such as self‐renewal – and are sensitive to different degrees of hypoxia. Failure to account for physiologically relevant oxygen concentrations in many studies may influence the current understanding of the roles of HIFαs. We also discuss how hypoxia and HIFαs contribute to CSC...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Drug resistance and cancer stem cells: the shared but distinct roles of hypoxia‐inducible factors HIF1α and HIF2α","attachmentId":112398065,"attachmentType":"pdf","work_url":"https://www.academia.edu/116201578/Drug_resistance_and_cancer_stem_cells_the_shared_but_distinct_roles_of_hypoxia_inducible_factors_HIF1%CE%B1_and_HIF2%CE%B1","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/116201578/Drug_resistance_and_cancer_stem_cells_the_shared_but_distinct_roles_of_hypoxia_inducible_factors_HIF1%CE%B1_and_HIF2%CE%B1"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="7360857" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/7360857/Loss_of_HIF_1%CE%B1_in_endothelial_cells_disrupts_a_hypoxia_driven_VEGF_autocrine_loop_necessary_for_tumorigenesis">Loss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="12976603" href="https://independent.academia.edu/tangnan">nan tang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer Cell, 2004</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Loss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis","attachmentId":48518168,"attachmentType":"pdf","work_url":"https://www.academia.edu/7360857/Loss_of_HIF_1%CE%B1_in_endothelial_cells_disrupts_a_hypoxia_driven_VEGF_autocrine_loop_necessary_for_tumorigenesis","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/7360857/Loss_of_HIF_1%CE%B1_in_endothelial_cells_disrupts_a_hypoxia_driven_VEGF_autocrine_loop_necessary_for_tumorigenesis"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="69780486" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/69780486/HIF_1_Independent_Mechanisms_Regulating_Metabolic_Adaptation_in_Hypoxic_Cancer_Cells">HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="107403809" href="https://independent.academia.edu/ShenHanLee">Shen-Han Lee</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cells, 2021</p><p class="ds-related-work--abstract ds2-5-body-sm">In solid tumours, cancer cells exist within hypoxic microenvironments, and their metabolic adaptation to this hypoxia is driven by HIF-1 transcription factor, which is overexpressed in a broad range of human cancers. HIF inhibitors are under pre-clinical investigation and clinical trials, but there is evidence that hypoxic cancer cells can adapt metabolically to HIF-1 inhibition, which would provide a potential route for drug resistance. Here, we review accumulating evidence of such adaptions in carbohydrate and creatine metabolism and other HIF-1-independent mechanisms that might allow cancers to survive hypoxia despite anti-HIF-1 therapy. These include pathways in glucose, glutamine, and lipid metabolism; epigenetic mechanisms; post-translational protein modifications; spatial reorganization of enzymes; signalling pathways such as Myc, PI3K-Akt, 2-hyxdroxyglutarate and AMP-activated protein kinase (AMPK); and activation of the HIF-2 pathway. All of these should be investigated in ...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells","attachmentId":79744748,"attachmentType":"pdf","work_url":"https://www.academia.edu/69780486/HIF_1_Independent_Mechanisms_Regulating_Metabolic_Adaptation_in_Hypoxic_Cancer_Cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/69780486/HIF_1_Independent_Mechanisms_Regulating_Metabolic_Adaptation_in_Hypoxic_Cancer_Cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="61233450" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/61233450/Hypoxia_signalling_in_cancer_and_approaches_to_enforce_tumour_regression">Hypoxia signalling in cancer and approaches to enforce tumour regression</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="66249376" href="https://independent.academia.edu/FredericDayan">Frederic Dayan</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Nature, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia signalling in cancer and approaches to enforce tumour regression","attachmentId":74335267,"attachmentType":"pdf","work_url":"https://www.academia.edu/61233450/Hypoxia_signalling_in_cancer_and_approaches_to_enforce_tumour_regression","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/61233450/Hypoxia_signalling_in_cancer_and_approaches_to_enforce_tumour_regression"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="97793890" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/97793890/Cancer_Cell_Metabolism_in_Hypoxia_Role_of_HIF_1_as_Key_Regulator_and_Therapeutic_Target">Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="115841092" href="https://unibas-it.academia.edu/SimonaTodisco">Simona Todisco</a></div><p class="ds-related-work--metadata ds2-5-body-xs">International Journal of Molecular Sciences, 2021</p><p class="ds-related-work--abstract ds2-5-body-sm">In order to meet the high energy demand, a metabolic reprogramming occurs in cancer cells. Its role is crucial in promoting tumor survival. Among the substrates in demand, oxygen is fundamental for bioenergetics. Nevertheless, tumor microenvironment is frequently characterized by low-oxygen conditions. Hypoxia-inducible factor 1 (HIF-1) is a pivotal modulator of the metabolic reprogramming which takes place in hypoxic cancer cells. In the hub of cellular bioenergetics, mitochondria are key players in regulating cellular energy. Therefore, a close crosstalk between mitochondria and HIF-1 underlies the metabolic and functional changes of cancer cells. Noteworthy, HIF-1 represents a promising target for novel cancer therapeutics. In this review, we summarize the molecular mechanisms underlying the interplay between HIF-1 and energetic metabolism, with a focus on mitochondria, of hypoxic cancer cells.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target","attachmentId":99319904,"attachmentType":"pdf","work_url":"https://www.academia.edu/97793890/Cancer_Cell_Metabolism_in_Hypoxia_Role_of_HIF_1_as_Key_Regulator_and_Therapeutic_Target","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/97793890/Cancer_Cell_Metabolism_in_Hypoxia_Role_of_HIF_1_as_Key_Regulator_and_Therapeutic_Target"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="106430548" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/106430548/HIF_Induces_Human_Embryonic_Stem_Cell_Markers_in_Cancer_Cells">HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="56321994" href="https://independent.academia.edu/HRuoholabaker">H. Ruohola-baker</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer Research, 2011</p><p class="ds-related-work--abstract ds2-5-body-sm">Low oxygen levels have been shown to promote self-renewal in many stem cells. In tumors, hypoxia is associated with aggressive disease course and poor clinical outcomes. Furthermore, many aggressive tumors have been shown to display gene expression signatures characteristic of human embryonic stem cells (hESC). We now tested whether hypoxia might be responsible for the hESC signature observed in aggressive tumors. We show that hypoxia, through hypoxia-inducible factor (HIF), can induce an hESC-like transcriptional program, including the induced pluripotent stem cell (iPSC) inducers, OCT4, NANOG, SOX2, KLF4, cMYC, and microRNA-302 in 11 cancer cell lines (from prostate, brain, kidney, cervix, lung, colon, liver, and breast tumors). Furthermore, nondegradable forms of HIFα, combined with the traditional iPSC inducers, are highly efficient in generating A549 iPSC-like colonies that have high tumorigenic capacity. To test potential correlation between iPSC inducers and HIF expression in...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells","attachmentId":105630774,"attachmentType":"pdf","work_url":"https://www.academia.edu/106430548/HIF_Induces_Human_Embryonic_Stem_Cell_Markers_in_Cancer_Cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/106430548/HIF_Induces_Human_Embryonic_Stem_Cell_Markers_in_Cancer_Cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":109838598,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":109838598,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_109838598" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="61201497" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/61201497/Impact_of_cyclic_hypoxia_on_HIF_1%CE%B1_regulation_in_endothelial_cells_new_insights_for_anti_tumor_treatments">Impact of cyclic hypoxia on HIF-1α regulation in endothelial cells - new insights for anti-tumor treatments</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="187740366" href="https://independent.academia.edu/VincentGregoire2">Vincent Gregoire</a></div><p class="ds-related-work--metadata ds2-5-body-xs">FEBS Journal, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Impact of cyclic hypoxia on HIF-1α regulation in endothelial cells - new insights for anti-tumor treatments","attachmentId":74318156,"attachmentType":"pdf","work_url":"https://www.academia.edu/61201497/Impact_of_cyclic_hypoxia_on_HIF_1%CE%B1_regulation_in_endothelial_cells_new_insights_for_anti_tumor_treatments","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/61201497/Impact_of_cyclic_hypoxia_on_HIF_1%CE%B1_regulation_in_endothelial_cells_new_insights_for_anti_tumor_treatments"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="1" data-entity-id="12024430" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/12024430/Hypoxia_induces_a_lipogenic_cancer_cell_phenotype_via_HIF1%CE%B1_dependent_and_independent_pathways">Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="17408628" href="https://oxford.academia.edu/FrancescaBuffa">Francesca Buffa</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Oncotarget, 2014</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways","attachmentId":46399850,"attachmentType":"pdf","work_url":"https://www.academia.edu/12024430/Hypoxia_induces_a_lipogenic_cancer_cell_phenotype_via_HIF1%CE%B1_dependent_and_independent_pathways","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/12024430/Hypoxia_induces_a_lipogenic_cancer_cell_phenotype_via_HIF1%CE%B1_dependent_and_independent_pathways"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="2" data-entity-id="73618162" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/73618162/Hypoxia_Inducible_Factor_down_regulation_cancer_and_cancer_stem_cells_CSCs_ongoing_success_stories">Hypoxia Inducible Factor down-regulation, cancer and cancer stem cells (CSCs): ongoing success stories</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="25334794" href="https://independent.academia.edu/RBenhida">Rachid Benhida</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Med. Chem. Commun., 2016</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia Inducible Factor down-regulation, cancer and cancer stem cells (CSCs): ongoing success stories","attachmentId":82069880,"attachmentType":"pdf","work_url":"https://www.academia.edu/73618162/Hypoxia_Inducible_Factor_down_regulation_cancer_and_cancer_stem_cells_CSCs_ongoing_success_stories","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/73618162/Hypoxia_Inducible_Factor_down_regulation_cancer_and_cancer_stem_cells_CSCs_ongoing_success_stories"><span class="ds2-5-text-link__content">View PDF</span><span 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data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/72844703/Hypoxia_induced_HIF_1_%CE%B1_expression_promotes_angiogenesis_tumor_budding_cell_survival_and_cell_proliferation_arrest_in_high_grade_tumor_budding_colorectal_carcinomas">Hypoxia induced HIF-1 α expression promotes angiogenesis , tumor budding cell survival and cell proliferation arrest in high-grade tumor budding colorectal carcinomas</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="147508507" href="https://independent.academia.edu/NataliePatel1">Natalie Patel</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2016</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia induced HIF-1 α 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href="https://www.academia.edu/15549361/Hypoxia_inducible_factor_1_modulates_gene_expression_in_solid_tumors_and_influences_both_angiogenesis_and_tumor_growth">Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="34705037" href="https://independent.academia.edu/IanStratford">Ian Stratford</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Proceedings of the National Academy of Sciences, 1997</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor 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