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We found that loss of HIF-1␣ inhibits a number of important parameters of EC behavior during angiogenesis: these include proliferation, chemotaxis, extracellular matrix penetration, and wound healing. Most strikingly, loss of HIF-1␣ in EC results in a profound inhibition of blood vessel growth in solid tumors. These phenomena are all linked to a decreased level of VEGF expression and loss of autocrine response of VEGFR-2 in HIF-1␣ null EC. We thus show that a HIF-1␣-driven, VEGF-mediated autocrine loop in EC is an essential component of solid tumor angiogenesis.","publication_date":"2004,,","publication_name":"Cancer Cell","grobid_abstract_attachment_id":"48518168"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Loss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [12976603]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; window.loswp.appleClientId = 'edu.academia.applesignon';</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":48518168,"attachmentType":"pdf"}"><img alt="First page of “Loss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/48518168/mini_magick20190203-5177-126qby.png?1549219091" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/assets/single_work_splash/adobe.icon-574afd46eb6b03a77a153a647fb47e30546f9215c0ee6a25df597a779717f9ef.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">Loss of HIF-1α in endothelial cells disrupts a hypoxia-driven VEGF autocrine loop necessary for tumorigenesis</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="12976603" href="https://independent.academia.edu/tangnan"><img alt="Profile image of nan tang" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />nan tang</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">2004, Cancer Cell</p><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">11 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 7360857; 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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="19383039" 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/19383039/The_hypoxic_response_of_tumors_is_dependent_on_their_microenvironment">The hypoxic response of tumors is dependent on their microenvironment</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="39646138" href="https://independent.academia.edu/HanspeterGerber">Hans-peter Gerber</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer Cell, 2003</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 hypoxic response of tumors is dependent on their microenvironment","attachmentId":40589305,"attachmentType":"pdf","work_url":"https://www.academia.edu/19383039/The_hypoxic_response_of_tumors_is_dependent_on_their_microenvironment","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/19383039/The_hypoxic_response_of_tumors_is_dependent_on_their_microenvironment"><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="105232962" 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/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">The Hypoxia-Associated Factor Switches Cells from HIF-1α- to HIF-2α-Dependent Signaling Promoting Stem Cell Characteristics, Aggressive Tumor Growth and Invasion</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="272254574" href="https://independent.academia.edu/GarthPowis">Garth Powis</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">Most solid tumors and their metastases experience periods of low oxygen or hypoxia, which is of major clinical significance as it promotes both tumor progression and resistance to therapy. 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="8" data-entity-id="25330830" 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/25330830/Role_of_Hypoxia_Inducible_Factor_1_in_Gastric_Cancer_Cell_Growth_Angiogenesis_and_Vessel_Maturation">Role of Hypoxia-Inducible Factor 1 in Gastric Cancer Cell Growth, Angiogenesis, and Vessel Maturation</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="45771235" href="https://independent.academia.edu/fanfan20">fan fan</a></div><p class="ds-related-work--metadata ds2-5-body-xs">JNCI Journal of the National Cancer Institute, 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":"Role of Hypoxia-Inducible Factor 1 in Gastric Cancer Cell Growth, Angiogenesis, and Vessel Maturation","attachmentId":45628799,"attachmentType":"pdf","work_url":"https://www.academia.edu/25330830/Role_of_Hypoxia_Inducible_Factor_1_in_Gastric_Cancer_Cell_Growth_Angiogenesis_and_Vessel_Maturation","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/25330830/Role_of_Hypoxia_Inducible_Factor_1_in_Gastric_Cancer_Cell_Growth_Angiogenesis_and_Vessel_Maturation"><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="88622472" 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/88622472/HIF_1%CE%B1_GPER_signaling_mediates_the_expression_of_VEGF_induced_by_hypoxia_in_breast_cancer_associated_fibroblasts_CAFs_">HIF-1α/GPER signaling mediates the expression of VEGF induced by hypoxia in breast cancer associated fibroblasts (CAFs)</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="32392644" href="https://independent.academia.edu/MSantolla">M. Santolla</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Breast Cancer Research, 2013</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-1α/GPER signaling mediates the expression of VEGF induced by hypoxia in breast cancer associated fibroblasts (CAFs)","attachmentId":92561310,"attachmentType":"pdf","work_url":"https://www.academia.edu/88622472/HIF_1%CE%B1_GPER_signaling_mediates_the_expression_of_VEGF_induced_by_hypoxia_in_breast_cancer_associated_fibroblasts_CAFs_","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/88622472/HIF_1%CE%B1_GPER_signaling_mediates_the_expression_of_VEGF_induced_by_hypoxia_in_breast_cancer_associated_fibroblasts_CAFs_"><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":48518168,"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":48518168,"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_48518168" 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. 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