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Cited by 1,340Cancer, Hypoxia, and MetabolismMechanisms of cancer metastasisCancer Cells and Metastasis

Hypoxic control of metastasis

Open access
Rankin, Erinn B., Giaccia, Amato J.·2016·Science
DOI 10.1126/science.aaf4405PMC PMC4898055
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Abstract

Metastatic disease is the leading cause of cancer-related deaths and involves critical interactions between tumor cells and the microenvironment. Hypoxia is a potent microenvironmental factor promoting metastatic progression. Clinically, hypoxia and the expression of the hypoxia-inducible transcription factors HIF-1 and HIF-2 are associated with increased distant metastasis and poor survival in a variety of tumor types. Moreover, HIF signaling in malignant cells influences multiple steps within the metastatic cascade. Here we review research focused on elucidating the mechanisms by which the hypoxic tumor microenvironment promotes metastatic progression. These studies have identified potential biomarkers and therapeutic targets regulated by hypoxia that could be incorporated into strategies aimed at preventing and treating metastatic disease.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes mechanisms by which hypoxia and HIF-1/HIF-2 signaling promote metastatic progression, from immune evasion and EMT to premetastatic niche formation and distant-site metabolic adaptation. It highlights candidate biomarkers and therapeutic targets, including AXL, LOX, exosomes, CKB, and PDK1.

Key findings

  • Metastatic disease is responsible for more than 90% of cancer-related deaths, and an estimated 50 to 60% of solid tumors contain regions of hypoxia and/or anoxia; clinically, hypoxia and HIF expression are associated with increased metastasis, therapy resistance, and poor survival.
  • HIF signaling influences multiple steps of the metastatic cascade, including immune evasion, EMT/invasion/migration, premetastatic niche formation, and growth/survival at distant sites; specific mediators discussed include AXL, LOX/LOXL2/4, exosomes, CKB, and PDK1.
  • In the liver, an oxygen gradient exists with periportal blood at 60 to 65 mm Hg and perivenous blood at 30 to 35 mm Hg; colon cancer cells adapt to hepatic hypoxia via CKB/phosphocreatine, and breast cancer liver metastases depend on glycolysis largely through the HIF-1 target PDK1.
  • High HIF-1 expression is associated with metastasis in gynecological, pancreatic, esophageal, lung, and prostate cancers, while HIF-2 expression is associated with distant metastasis in small cell lung and breast cancers; experimentally, HIF overexpression promotes metastasis and HIF inactivation decreases metastatic potential.

Methods

  • Design: narrative review of the literature on hypoxia, HIF signaling, and metastasis.
  • Data or sample: no primary dataset; the paper synthesizes clinical observations and preclinical models, including human tumor immunohistochemical analyses and mouse metastasis studies.
  • Main analysis: thematic synthesis of mechanisms by which hypoxia and HIF-dependent signaling regulate immune evasion, EMT, premetastatic niche formation, and distant-site colonization.

Limitations

  • Stated limitations: Not stated in the paper.
  • Evident limitations: as a narrative review, it does not describe a systematic search strategy, inclusion criteria, or quantitative synthesis, so selection bias is possible.
  • Evident limitations: many mechanistic conclusions rely on preclinical models and association studies in human tumors, which may not establish causality in patients.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1126/science.aaf4405

Cites

116 of 116 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 153 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Hypoxia and activation of HIF signaling influence multiple steps within the metastatic cascade, including invasion and migration, intravasation and extravasation, establishment of the premetastatic niche, and survival and growth at the distant site.

    “Hypoxia and activation of HIF signaling influence multiple steps within the metastatic cascade, including invasion and migration, intravasation and extravasation, and establishment of the premetastatic niche, as well as survival and growth at the distant site”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [48] De Bock K Mazzone M Carmeliet P Nat. Rev. Clin. Oncol 2011 8 393 404 21629216 source

      Not checked in the free run.

    • cites [49] Semenza GL Biochim. Biophys. Acta 2016 1863 382 391 26079100 PMC4678039 source

      Not checked in the free run.

  • Premisecitation

    HIF-1 and HIF-2 coordinate the adaptive cellular response to low oxygen tensions by activating gene expression programs controlling glucose uptake, metabolism, angiogenesis, erythropoiesis, cell proliferation, differentiation, and apoptosis.

    “The hypoxia-inducible transcription factors HIF-1 and HIF-2 coordinate the adaptive cellular response to low oxygen tensions by activating gene expression programs controlling glucose uptake, metabolism, angiogenesis, erythropoiesis, cell proliferation, differentiation, and apoptosis”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Semenza GL Cell 2012 148 399 408 22304911 PMC3437543 source

      Not checked in the free run.

  • Interpretationreasoning

    Hypoxia is a potent microenvironmental factor promoting metastatic progression.

    “Hypoxia is a potent microenvironmental factor promoting metastatic progression.”
    Quote in the paperSubstantial claim
  • Interpretationreasoning

    HIF signaling in malignant cells influences multiple steps within the metastatic cascade.

    “HIF signaling in malignant cells influences multiple steps within the metastatic cascade.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Hydroxylation of HIF-α allows VHL to bind HIF-α and target it for proteasomal degradation.

    “This hydroxylation event allows the von Hippel–Lindau tumor suppressor protein (VHL), the substrate recognition component of an E3 ubiquitin ligase complex, to bind to HIF-α and target it for proteasomal degradation”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [10] Jaakkola P Science 2001 292 468 472 11292861 source

      Not checked in the free run.

    • cites [11] Ivan M Science 2001 292 464 468 11292862 source

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      Not checked in the free run.

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      Not checked in the free run.

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      Not checked in the free run.

  • May combine two claims. 27
  • Classified as probably not a substantial claim. 5

  • May combine two claims.

    Premisecitation

    Clinically, hypoxia is associated with HIF activation, metastasis, resistance to chemotherapy and radiotherapy, and poor patient survival.

    “Clinically, hypoxia is associated with HIF activation, metastasis, and resistance to chemotherapy and radiotherapy, as well as poor patient survival”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [4] Rankin EB Giaccia AJ Cell Death Differ 2008 15 678 685 18259193 PMC3050610 source

      Not checked in the free run.

    • cites [5] Schindl M Clin. Cancer Res 2002 8 1831 1837 12060624

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [6] Yamamoto Y Breast Cancer Res. Treat 2008 110 465 475 17805961 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HIF-1 and HIF-2 expression are associated with increased distant metastasis and poor survival in a variety of tumor types.

    “Clinically, HIF-1 and HIF-2 are highly expressed in primary tumors and metastases.”
    • Also stated in: § Hypoxic signaling · hedged
      “increased HIF expression is often linked with increased patient mortality in a variety of human cancers”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [41] Semenza GL Oncogene 2010 29 625 634 19946328 PMC2969168 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    50 to 60% of solid tumors contain regions of hypoxia and/or anoxia.

    “It has been estimated that 50 to 60% of solid tumors contain regions of hypoxia and/or anoxia”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Vaupel P Mayer A Cancer Metastasis Rev 2007 26 225 239 17440684 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mutations in SDH or FH cause accumulation of cytosolic succinate or fumarate, which inhibits prolyl hydroxylases and leads to HIF stabilization under normoxic conditions.

    “In tumor cells, mutations in the genes encoding succinate dehydrogenase (SDH) or fumarate hydratase (FH) cause the accumulation of cytosolic succinate or fumarate; this inhibits the activity of prolyl hydroxylases and leads to HIF stabilization under normoxic conditions”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Kaelin WG Jr. Cold Spring Harb. Symp. Quant. Biol 2011 76 335 345 22089927 PMC4197849 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    EGLN 1-3 activity and HIF-α stability are affected by iron availability and can be inhibited by Krebs cycle intermediates succinate and fumarate.

    “As a result, EGLN 1–3 activity and HIF-α stability are affected by iron availability and can be inhibited by Krebs cycle intermediates, including succinate and fumarate, which compete with 2-oxoglutarate”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [18] Pan Y Mol. Cell. Biol 2007 27 912 925 17101781 PMC1800695 source

      Not checked in the free run.

    • cites [19] Nandal A Cell Metab 2011 14 647 657 22055506 PMC3361910 source

      Not checked in the free run.

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      Not checked in the free run.

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      Not checked in the free run.

    • cites [22] Kaelin WG Jr. Cold Spring Harb. Symp. Quant. Biol 2011 76 335 345 22089927 PMC4197849 source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    HIF-1 and HIF-2 allow cells to survive and adapt to low oxygen tensions and confer changes in both tumor and host that promote metastasis.

    “these factors allow cells to survive and adapt to low oxygen tensions, as well as confer changes in both and host that promote metastasis”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    Under hypoxic conditions, PHD activity is inhibited, resulting in HIF-α stabilization and translocation to the nucleus.

    “Under hypoxic conditions, PHD activity is inhibited, resulting in HIF-α stabilization and translocation to the nucleus.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    WSB1 expression in tumor cells leads to HIF stabilization under normoxic and hypoxic conditions and correlates with metastasis in cancer patients.

    “WSB1 expression in tumor cells leads to HIF stabilization under normoxic and hypoxic conditions and correlates with metastasis in cancer patients”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Kim JJ Genes Dev 2015 29 2244 2257 26545811 PMC4647558 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Genetic inactivation of VHL is thought to be an early event in the pathogenesis of ccRCC.

    “Although genetic inactivation of VHL is thought to be an early event in the pathogenesis of ccRCC”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Genetic mutations or epigenetic inactivation of VHL causes VHL disease, which is associated with constitutive activation of HIF-1 and HIF-2 and development of highly vascularized tumors.

    “Genetic mutations or epigenetic inactivation of VHL causes VHL disease, which is associated with constitutive activation of HIF-1 and HIF-2 and the development of highly vascularized tumors”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Both HIF-α mRNA transcription and translation are regulated by TORC1 activity.

    “Both HIF-α mRNA transcription and translation are regulated by TORC1 activity”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Kaelin WG Jr. Cold Spring Harb. Symp. Quant. Biol 2011 76 335 345 22089927 PMC4197849 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Renal cell carcinoma is a major cause of morbidity in VHL patients, owing to the ability of these tumors to metastasize to other tissue sites.

    “Renal cell carcinoma is a major cause of morbidity in VHL patients, owing to the ability of these tumors to metastasize to other tissue sites”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Lonser RR Lancet 2003 361 2059 2067 12814730

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    UCHL1 is associated with HIF-1 and distant metastasis in cancer patients.

    “UCHL1 is associated with HIF-1 and distant metastasis in cancer patients”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Goto Y Nat. Commun 2015 6 6153 25615526 PMC4317501 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HIF-1 mRNA translation can be enhanced under normoxic and hypoxic conditions through the binding of YB-1, leading to increased HIF-1 protein and prometastatic activity in sarcoma cells.

    “HIF-1 mRNA translation can be enhanced under normoxic and hypoxic conditions through the binding of YB-1, an RNA and DNA binding protein; this leads to increased HIF-1 protein and prometastatic activity in sarcoma cells”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] El-Naggar AM Cancer Cell 2015 27 682 697 25965573

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Respiratory hyperoxia is associated with a decrease in intratumoral hypoxia and an immunopermissive tumor microenvironment characterized by abundant CD8+ T cell infiltration and decreased regulatory T cell infiltration.

    “respiratory hyperoxia was associated with a decrease in intratumoral hypoxia and an immunopermissive tumor microenvironment characterized by abundant CD8+ T cell infiltration and decreased regulatory T cell infiltration”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Hatfield SM Sci. Transl. Med 2015 7 277ra30 PMC4641038 25739764 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In preclinical models, respiratory hyperoxia (60% O2) can promote tumor regression, reduce metastatic disease, and prolong animal survival.

    “In preclinical models, respiratory hyperoxia (60% O2) can promote tumor regression, reduce metastatic disease, and prolong animal survival”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Hatfield SM Sci. Transl. Med 2015 7 277ra30 PMC4641038 25739764 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tregs promote immune tolerance and angiogenesis, which supports metastatic tumor growth.

    “Once in the tumor microenvironment, Tregs promote immune tolerance and angiogenesis, which supports metastatic tumor growth”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [60] Facciabene A Nature 2011 475 226 230 21753853 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Hypoxic signaling in MDSCs and macrophages directly contributes to tumor progression by promoting an immunosuppressive phenotype and stimulating angiogenesis.

    “Hypoxic signaling in MDSCs and macrophages directly contributes to tumor progression by promoting an immunosuppressive phenotype and stimulating angiogenesis”
    Quote in the paperSubstantial claim0 of 4 sources checked
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      Not checked in the free run.

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  • May combine two claims.

    Premisecitation

    Hypoxic signaling can promote resistance to T cell-mediated killing by increasing expression of PD-L1 on tumor cells and myeloid-derived suppressor cells, and by enhancing CTLA-4 expression on CD8+ T cells.

    “Hypoxic signaling can promote resistance to T cell–mediated killing by increasing the expression of programmed death–ligand 1 (PD-L1) on tumor cells and myeloid-derived suppressor cells (MDSCs), and by enhancing CTLA-4 expression on CD8+ T cells”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [57] Palazon A Goldrath AW Nizet V Johnson RS Immunity 2014 41 518 528 25367569 PMC4346319 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Cell-cell adhesions are mediated primarily by cadherin proteins expressed at intercellular junctions.

    “Cell-cell adhesions are mediated primarily by cadherin proteins expressed at intercellular junctions”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] Cavallaro U Christofori G Nat. Rev. Cancer 2004 4 118 132 14964308

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  • May combine two claims.

    Premisecitation

    Loss of AXL does not appear to have deleterious effects on embryonic development or normal adult tissue function in mice.

    “Loss of AXL does not appear to have deleterious effects on embryonic development or normal adult tissue function in mice”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [87] Lu Q Nature 1999 398 723 728 10227296 source

      Not checked in the free run.

    • cites [88] Angelillo-Scherrer A Nat. Med 2001 7 215 221 11175853 source

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    Premisecitation

    Biological inhibitors of AXL, such as soluble AXL decoy receptors, are specific and are not associated with normal tissue or hematologic toxicities in mice.

    “biological inhibitors of AXL, such as soluble AXL decoy receptors, are specific and are not associated with normal tissue or hematologic toxicities in mice”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    • cites [89] Kariolis MS Nat. Chem. Biol 2014 10 977 983 25242553 PMC4372605

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    LOX promotes tumor cell proliferation, invasion, and angiogenesis.

    “Given that LOX also promotes tumor cell proliferation, invasion, and angiogenesis, LOX is an attractive therapeutic target for cancer therapy (97).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [97] Cox TR Gartland A Erler JT Cancer Res 2016 76 188 192 26732355

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    Premisecitation

    IL-6 secretion by the tumor activates STAT3 signaling in LECs localized within the lymph node and lung to promote CCL5-mediated recruitment of CCR5-positive breast cancer cells into the lymphatic system and VEGF-mediated lung vascular permeability and lymph node angiogenesis.

    “IL-6 secretion by the tumor activates signal transducer and activator of transcription 3 (STAT3) signaling in LECs localized within the lymph node and lung to promote (i) CCL5-mediated recruitment of CCR5-positive breast cancer cells into the lymphatic system and (ii) VEGF-mediated lung vascular permeability and lymph node angiogenesis (98).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [98] Lee E Nat. Commun 2014 5 4715 25178650 PMC4351998 source

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    Premisecitation

    Tumor-derived exosomes preferentially localize to sites of metastasis including liver, lung, and bone marrow, where they promote vascular permeability and increase BMDC recruitment.

    “Moreover, tumor-derived exosomes preferentially localize to sites of metastasis, including liver, lung, and bone marrow, where they promote vascular permeability and increase BMDC recruitment (101–104).”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [101] Peinado H Nat. Med 2012 18 883 891 22635005 PMC3645291 source

      Not checked in the free run.

    • cites [102] Costa-Silva B Nat. Cell Biol 2015 17 816 826 25985394 PMC5769922 source

      Not checked in the free run.

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    • cites [104] Umezu T Blood 2014 124 3748 3757 25320245 PMC4263983 source

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  • May combine two claims.

    Premisecitation

    Hepatocytes that perform glucose or fatty acid oxidation are located in the aerobic periportal zone, whereas oxygen-independent metabolic functions such as glucose uptake, glycolysis, and fatty acid synthesis are predominantly performed by perivenous hepatocytes.

    “Because oxygen is an essential electron acceptor for oxidative metabolism, hepatocytes that perform glucose or fatty acid oxidation are located in the aerobic periportal zone, whereas oxygen-independent metabolic functions such as glucose uptake, glycolysis, and fatty acid synthesis are predominantly performed by perivenous hepatocytes (108).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [108] Jungermann K Semin. Liver Dis 1988 8 329 341 3062788

      Not checked in the free run.

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    Premisecitation

    The partial pressure of oxygen in periportal blood is 60 to 65 mm Hg and in perivenous blood is 30 to 35 mm Hg.

    “The partial pressure of oxygen in periportal blood is 60 to 65 mm Hg and in the perivenous blood it is 30 to 35 mm Hg (107).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [107] Jungermann K Kietzmann T Hepatology 2000 31 255 260 10655244

      Not checked in the free run.

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    Premisecitation

    VEGF-A is a proangiogenic factor produced by tumor cells that stimulates recruitment and proliferation of endothelial cells, as well as promoting pericyte proliferation and migration.

    “VEGF-A is a proangiogenic factor produced by tumor cells that stimulates the recruitment and proliferation of endothelial cells, as well as promoting pericyte proliferation and migration (113).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [113] Joyce JA Pollard JW Nat. Rev. Cancer 2009 9 239 252 19279573 PMC3251309 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Hepatic hypoxia is a barrier for colon cancer cells early in metastatic dissemination, and cells overcome this metabolic stress by generating ATP from phosphocreatine reserves.

    “suggesting that hepatic hypoxia is a barrier for colon cancer cells early in metastatic dissemination and that cells overcome this metabolic stress by generating ATP from phosphocreatine reserves (Fig. 3) (109).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [109] Loo JM Cell 2015 160 393 406 25601461 PMC4312495 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    VEGF-A is a well-established HIF target, and its expression is induced by HIF signaling in both primary tumors and metastases.

    “VEGF-A is a well-established HIF target, and its expression is induced by HIF signaling in both primary tumors and metastases (114).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [114] Maxwell PH Proc. Natl. Acad. Sci. U.S.A 1997 94 8104 8109 9223322 PMC21564 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    AXL is a critical mediator of HIF-dependent invasion and metastasis and a potential therapeutic target for prevention and treatment of metastatic disease.

    “Recent work has identified the receptor tyrosine kinase, AXL, as a critical mediator of HIF-dependent invasion and metastasis, as well as a potential therapeutic target for the prevention and treatment of metastatic disease.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Recent studies have begun to highlight diverse mechanisms by which hypoxia and HIF-dependent signaling promote metastatic tumor progression.

    “In summary, recent studies have begun to highlight the diverse mechanisms by which hypoxia and HIF-dependent signaling promote metastatic tumor progression.”
    Quote in the paperNot a substantial claim
32 of 32

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Each contradiction between two passages listed here was confirmed by an independent check.

  • Glycolytic liver zone identified inconsistently

    Minor

    The paper first places glycolysis predominantly in perivenous hepatocytes, but later attributes the liver's glycolytic phenotype to periportal regions.

1 of 1

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Related

Authors
Rankin, E. B., & Giaccia, A. J.
Affiliations
Stanford Medicine (US)
Corresponding author
Giaccia, Amato J.
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2016-04-08
Volume
352
Issue
6282
Pages
175-180
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aaf4405
PMC
PMC4898055
OpenAlex
W2323751645
Semantic Scholar
7c7208ae7f676afe4b7ee95982fba82e04f585f9
Cited by
1,340
References
116
Citations by year
2026: 98 · 2025: 117 · 2024: 127 · 2023: 119 · 2022: 191 · 2021: 186 · 2020: 160 · 2019: 143 · 2018: 87 · 2017: 85 · 2016: 26 · 2015: 1
FWCI
47.32
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH (CA-198291, CA-67166, CA-197713)
  • Silicon Valley Foundation
  • Sydney Frank Foundation
  • Kimmelman Fund
  • Department of Defense Ovarian Cancer Research Academy (OC140611)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
tumor hypoxia, metastasis, hypoxia-inducible factor, HIF-1, HIF-2, tumor microenvironment, metastatic progression, biomarkers, therapeutic target, cancer therapy
MeSH terms
Endothelial PAS Domain-Containing Protein 1, Animals, Cell Movement, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Radiation Tolerance, Biomarkers, Tumor, Signal Transduction, Cell Hypoxia, Disease Progression, Drug Resistance, Neoplasm, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, Epithelial-Mesenchymal Transition, Tumor Microenvironment

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