The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
HIF‐1α is required for solid tumor formation and embryonic vascularization
Open accessAbstract
The transcriptional response to lowered oxygen levels is mediated by the hypoxia-inducible transcription factor (HIF-1), a heterodimer consisting of the constitutively expressed aryl hydrocarbon receptor nuclear translocator (ARNT) and the hypoxic response factor HIF-1alpha. To study the role of the transcriptional hypoxic response in vivo we have targeted the murine HIF-1alpha gene. Loss of HIF-1alpha in embryonic stem (ES) cells dramatically retards solid tumor growth; this is correlated with a reduced capacity to release the angiogenic factor vascular endothelial growth factor (VEGF) during hypoxia. HIF-1alpha null mutant embryos exhibit clear morphological differences by embryonic day (E) 8.0, and by E8.5 there is a complete lack of cephalic vascularization, a reduction in the number of somites, abnormal neural fold formation and a greatly increased degree of hypoxia (measured by the nitroimidazole EF5). These data demonstrate the essential role of HIF-1alpha in controlling both embryonic and tumorigenic responses to variations in microenvironmental oxygenation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Vascularization is severely impaired in HIF1A -/- (Carmeliet et al., 1998;Ryan et al., 1998) and HIF2A -/- (Peng et al., 2000) mice.”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Ryan et al., 1998
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis
Shweiki, D., Itin, A., Soffer, D., & Keshet, E. (1992) · Nature · doi:10.1038/359843a0 · Cited by 4,617
Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
Forsythe, J. A., Jiang, B.-H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., & Semenza, G. L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4604 · Cited by 3,981
Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours
Graeber, T. G., Osmanian, C., Jacks, T., Housman, D. E., Koch, C. J., Lowe, S. W., & Giaccia, A. J. (1996) · Nature · doi:10.1038/379088a0 · Cited by 2,300
Ema, M., Taya, S., Yokotani, N., Sogawa, K., Matsuda, Y., & Fujii-Kuriyama, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4273 · Cited by 1,016
Semenza, G. L., Nejfelt, M. K., Chi, S. M., & Antonarakis, S. E. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.13.5680 · Cited by 990
Maltepe, E., Schmidt, J. V., Baunoch, D., Bradfield, C. A., & Simon, M. C. (1997) · Nature · doi:10.1038/386403a0 · Cited by 781
Research works printed but not linked: 44
- Akazawa S, Unterman T and Metzger BE (1994) Glucose metabolism in separated embryos and investing membranes during organogenesis in the rat. Metabolism, 43, 830–835. · DOI
- Banai S, Shweiki D, Pinson A, Chandra M, Lazarovici G and Keshet E (1994) Upregulation of vascular endothelial growth factor expression induced by myocardial ischaemia: implications for coronary angiogenesis. Cardiovasc Res, 28, 1176–1179. · DOI
- Blanchard KL, Fandrey J, Goldberg MA and Bunn HF (1993) Regulation of the erythropoietin gene. Stem Cells, 11 Suppl. 1, 1–7. · DOI
- Bonnerot C and Nicolas J‐F (1993) Application of LacZ gene fusions to post‐implantation development. In Wasserman,P. and DePamphilis,M.L. (eds), Guide to Techniques in Mouse Development. Academic Press, New York, pp. 451–469. · DOI
- Brown JM and Giaccia AJ (1994) Tumour hypoxia: the picture has changed in the 1990s. Int J Radiat Biol, 65, 95–102. · DOI
- Bunn HF and Poyton RO (1996) Oxygen sensing and molecular adaptation to hypoxia. Physiol Rev, 76, 839–885. · DOI
- Carmeliet P et al. (1996) Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature, 380, 435–439. · DOI
- Dachs GU, Patterson AV, Firth JD, Ratcliffe PJ, Townsend KM, Stratford IJ and Harris AL (1997) Targeting gene expression to hypoxic tumor cells. Nature Med, 3, 515–520. · DOI
- Damert A, Machein M, Breier G, Fujita MQ, Hanahan D, Risau W and Plate KH (1997) Up‐regulation of vascular endothelial growth factor expression in a rat glioma is conferred by two distinct hypoxia‐driven mechanisms. Cancer Res, 57, 3860–3864.
- Fernandez‐Salguero P et al. (1995) Immune system impairment and hepatic fibrosis in mice lacking the dioxin‐binding Ah receptor. Science, 268, 722–726. · DOI · Paper page
- Ferrara N, Carver‐Moore K, Chen H, Dowd M, Lu L, O'Shea KS, Powell‐Braxton L, Hillan KJ and Moore MW (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature, 380, 439–442. · DOI
- Finkenzeller G, Technau A and Marme D (1995) Hypoxia‐induced transcription of the vascular endothelial growth factor gene is independent of functional AP‐1 transcription factor. Biochem Biophys Res Commun, 208, 432–439. · DOI
- Gassmann M, Kvietikova I, Rolfs A and Wenger RH (1997) Oxygen‐ and dioxin‐regulated gene expression in mouse hepatoma cells. Kidney Int, 51, 567–574. · DOI
- Hirose K et al. (1996) cDNA cloning and tissue‐specific expression of a novel basic helix–loop–helix/PAS factor (Arnt2) with close sequence similarity to the aryl hydrocarbon receptor nuclear translocator (Arnt). Mol Cell Biol, 16, 1706–1713. · DOI
- Hogenesch JB, Chan WK, Jackiw VH, Brown RC, Gu YZ, Pray‐Grant M, Perdew GH and Bradfield CA (1997) Characterization of a subset of the basic‐helix–loop–helix‐PAS superfamily that interacts with components of the dioxin signaling pathway. J Biol Chem, 272, 8581–8593. · DOI
- Hunter ESR and Tugman JA (1995) Inhibitors of glycolytic metabolism affect neurulation‐staged mouse conceptuses in vitro. Teratology, 52, 317–323. · DOI
- Ikeda E, Achen MG, Breier G and Risau W (1995) Hypoxia‐induced transcriptional activation and increased mRNA stability of vascular endothelial growth factor in C6 glioma cells. J Biol Chem, 270, 19761–19766. · DOI
- Ladoux A and Frelin C (1993) Hypoxia is a strong inducer of vascular endothelial growth factor mRNA expression in the heart. Biochem Biophys Res Commun, 195, 1005–1010. · DOI
- Lee J, Siemann DW, Koch CJ and Lord EM (1996) Direct relationship between radiobiological hypoxia in tumors and monoclonal antibody detection of EF5 cellular adducts. Int J Cancer, 67, 372–378. · DOI
- Levy AP, Levy NS, Wegner S and Goldberg MA (1995) Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem, 270, 13333–13340. · DOI
- Levy AP, Levy NS and Goldberg MA (1996) Post‐transcriptional regulation of vascular endothelial growth factor by hypoxia. J Biol Chem, 271, 2746–2753. · DOI · Paper page
- Liu Y, Cox SR, Morita T and Kourembanas S (1995) Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5′ enhancer. Circ Res, 77, 638–643. · DOI
- Lord EM, Harwell L and Koch CJ (1993) Detection of hypoxic cells by monoclonal antibody recognizing 2‐nitroimidazole adducts. Cancer Res, 53, 5721–5726.
- Matsumoto K, Akazawa S, Ishibashi M, Trocino RA, Matsuo H, Yamasaki H, Yamaguchi Y, Nagamatsu S and Nagataki S (1995) Abundant expression of GLUT1 and GLUT3 in rat embryo during the early organogenesis period. Biochem Biophys Res Commun, 209, 95–102. · DOI
- Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S and Papaioannou VE (1992) RAG‐1‐deficient mice have no mature B and T lymphocytes. Cell, 68, 869–877. · DOI
- Mortensen RM, Conner DA, Chao S, Geisterfer‐Lowrance AA and Seidman JG (1992) Production of homozygous mutant ES cells with a single targeting construct. Mol Cell Biol, 12, 2391–2395.
- Nagy A and Rossant J (1992) Production of completely ES‐cell derived fetuses. In Joyner,A. (ed.), Gene Targeting: A Practical Approach. IRL Press at Oxford University Press, Oxford, UK.
- Papaioannou VE and Johnson RS (1992) Production of chimeras and genetically defined offspring from targeted ES cells. In Joyner,A. (ed.), Gene Targeting: A Practical Approach. IRL Press at Oxford University Press, Oxford, UK.
- Pe'er J, Shweiki D, Itin A, Hemo I, Gnessin H and Keshet E (1995) Hypoxia‐induced expression of vascular endothelial growth factor by retinal cells is a common factor in neovascularizing ocular diseases. Lab Invest, 72, 638–645.
- Potgens AJ, Lubsen NH, van Altena MC, Schoenmakers JG, Ruiter DJ and de Waal RM (1995) Vascular permeability factor expression influences tumor angiogenesis in human melanoma lines xenografted to nude mice. Am J Pathol, 146, 197–209.
- Rowlands JC and Gustafsson JA (1997) Aryl hydrocarbon receptor‐mediated signal transduction. Crit Rev Toxicol, 27, 109–134. · DOI
- Schlaeger TM, Qin Y, Fujiwara Y, Magram J and Sato TN (1995) Vascular endothelial cell lineage‐specific promoter in transgenic mice. Development, 121, 1089–1098. · DOI
- Schmidt JV, Su GH, Reddy JK, Simon MC and Bradfield CA (1996) Characterization of a murine Ahr null allele: involvement of the Ah receptor in hepatic growth and development. Proc Natl Acad Sci USA, 93, 6731–6736. · DOI
- Semenza GL and Wang GL (1992) A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol Cell Biol, 12, 5447–5454.
- Semenza GL, Roth PH, Fang HM and Wang GL (1994) Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia‐inducible factor 1. J Biol Chem, 269, 23757–23763. · DOI
- Shepard TH, Tanimura T and Park HW (1997) Glucose absorption and utilization by rat embryos. Int J Dev Biol, 41, 307–314. · DOI
- Shima DT, Deutsch U and D'Amore PA (1995) Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability. FEBS Lett, 370, 203–208. · DOI
- Stone J, Itin A, Alon T, Pe'er J, Gnessin H, Chan‐Ling T and Keshet E (1995) Development of retinal vasculature is mediated by hypoxia‐induced vascular endothelial growth factor (VEGF) expression by neuroglia. J Neurosci, 15, 4738–4747. · DOI
- Swanson HI and Bradfield CA (1993) The AH‐receptor: genetics, structure and function. Pharmacogenetics, 3, 213–230. · DOI
- Tian H, McKnight SL and Russell DW (1997) Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev, 11, 72–82. · DOI · Paper page
- Wang GL and Semenza GL (1993a) Characterization of hypoxia‐inducible factor 1 and regulation of DNA binding activity by hypoxia. J Biol Chem, 268, 21513–21518. · DOI
- Wang GL and Semenza GL (1993b) General involvement of hypoxia‐inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci USA, 90, 4304–4308. · DOI · Paper page
- Wang GL and Semenza GL (1995) Purification and characterization of hypoxia‐inducible factor 1. J Biol Chem, 270, 1230–1237. · DOI
- Wang GL, Jiang BH, Rue EA and Semenza GL (1995) Hypoxia‐inducible factor 1 is a basic‐helix–loop–helix‐PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA, 92, 5510–5514. · DOI · Paper page
Cited by
Sorted by citations
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
Hypoxia — a key regulatory factor in tumour growth
Harris, A. L. (2002) · Nature Reviews Cancer · doi:10.1038/nrc704 · Cited by 5,177
Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway.
Kaelin, W. G., & Ratcliffe, P. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.04.009 · Cited by 3,251
Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation
Lunt, S. Y., & Vander Heiden, M. G. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154237 · Cited by 3,057
A conserved family of prolyl-4-hydroxylases that modify HIF
Bruick, R. K., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1066373 · Cited by 2,549
Regulation of angiogenesis by hypoxia: role of the HIF system
Pugh, C. W., & Ratcliffe, P. J. (2003) · Nature Medicine · doi:10.1038/nm0603-677 · Cited by 2,520
HIF-1α is essential for myeloid cell-mediated inflammation
Cramer, T., Yamanishi, Y., Clausen, B. E., Förster, I., Pawlinski, R., Mackman, N., Haase, V. H., Jaenisch, R., Corr, M., Nizet, V., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00154-5 · Cited by 2,046
Self-citationChandel, N. S., McClintock, D. S., Feliciano, C. E., Wood, T. M., Melendez, J. A., Rodriguez, A. M., & Schumacker, P. T. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001914200 · Cited by 2,000
Regulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914
HIF-1: mediator of physiological and pathophysiological responses to hypoxia
Semenza, G. L. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.4.1474 · Cited by 1,822
Signaling mechanisms of the epithelial-mesenchymal transition
Gonzalez, D. M., & Medici, D. (2014) · Science Signaling · doi:10.1126/scisignal.2005189 · Cited by 1,721
HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Keith, B., Johnson, R. S., & Simon, M. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3183 · Cited by 1,693
Self-citationNF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α
Rius, J., Guma, M., Schachtrup, C., Akassoglou, K., Zinkernagel, A. S., Nizet, V., Johnson, R. S., Haddad, G. G., & Karin, M. (2008) · Nature · doi:10.1038/nature06905 · Cited by 1,614
Self-citationAsparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002) · Science · doi:10.1126/science.1068592 · Cited by 1,558
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386
Direct regulation of TWIST by HIF-1α promotes metastasis
Yang, M.-H., Wu, M.-Z., Chiou, S.-H., Chen, P.-M., Chang, S.-Y., Liu, C.-J., Teng, S.-C., & Wu, K.-J. (2008) · Nature Cell Biology · doi:10.1038/ncb1691 · Cited by 1,345
Talks, K. L., Turley, H., Gatter, K. C., Maxwell, P. H., Pugh, C. W., Ratcliffe, P. J., & Harris, A. L. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64554-3 · Cited by 1,312
Laughner, E., Taghavi, P., Chiles, K., Mahon, P. C., & Semenza, G. L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.12.3995-4004.2001 · Cited by 1,256
Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1
Manalo, D. J., Rowan, A., Lavoie, T., Natarajan, L., Kelly, B. D., Ye, S. Q., Garcia, J. G. N., & Semenza, G. L. (2005) · Blood · doi:10.1182/blood-2004-07-2958 · Cited by 1,154
Wenger, R. H. (2002) · The FASEB Journal · doi:10.1096/fj.01-0944rev · Cited by 1,135
Oncogenic alterations of metabolism
Dang, C. V., & Semenza, G. L. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01344-9 · Cited by 1,106
Simsek, T., Kocabas, F., Zheng, J., DeBerardinis, R. J., Mahmoud, A. I., Olson, E. N., Schneider, J. W., Zhang, C. C., & Sadek, H. A. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.07.011 · Cited by 1,101
Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1α
Ravi, R., Mookerjee, B., Bhujwalla, Z. M., Sutter, C. H., Artemov, D., Zeng, Q., Dillehay, L. E., Madan, A., Semenza, G. L., & Bedi, A. (2000) · Genes & Development · doi:10.1101/gad.14.1.34 · Cited by 967
Isaacs, J. S., Jung, Y. J., Mole, D. R., Lee, S., Torres-Cabala, C., Chung, Y.-L., Merino, M., Trepel, J., Zbar, B., Toro, J., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.06.017 · Cited by 958
Raval, R. R., Lau, K. W., Tran, M. G. B., Sowter, H. M., Mandriota, S. J., Li, J.-L., Pugh, C. W., Maxwell, P. H., Harris, A. L., & Ratcliffe, P. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.13.5675-5686.2005 · Cited by 940
Weidemann, A., & Johnson, R. S. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.12 · Cited by 941
Self-citationRegulation of Oxygen Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (2009) · Physiology · doi:10.1152/physiol.00045.2008 · Cited by 926
Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology
Semenza, G. L. (2001) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(01)02090-1 · Cited by 930
HIF-1 and human disease: one highly involved factor
Semenza, G. L. (2000) · Genes & Development · doi:10.1101/gad.14.16.1983 · Cited by 909
Guzy, R. D., & Schumacker, P. T. (2006) · Experimental Physiology · doi:10.1113/expphysiol.2006.033506 · Cited by 881
Molecular basis of the VHL hereditary cancer syndrome
Kaelin, W. G. (2002) · Nature Reviews Cancer · doi:10.1038/nrc885 · Cited by 865
Signal transduction to hypoxia-inducible factor 1
Semenza, G. L. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)01168-1 · Cited by 860
Loss of PTEN facilitates HIF-1-mediated gene expression
Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A. R., Ryan, H. E., Johnson, R. S., Jefferson, A. B., et al. (2000) · Genes & Development · doi:10.1101/gad.14.4.391 · Cited by 840
Self-citationThe role of hypoxia-inducible factors in tumorigenesis
Rankin, E. B., & Giaccia, A. J. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.21 · Cited by 806
Regulation of erythropoiesis by hypoxia-inducible factors
Haase, V. H. (2013) · Blood Reviews · doi:10.1016/j.blre.2012.12.003 · Cited by 787
Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology
Li, J.-M., & Shah, A. M. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00124.2004 · Cited by 773
Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein
Kondo, K., Klco, J., Nakamura, E., Lechpammer, M., & Kaelin, W. G. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00043-0 · Cited by 761
Holmquist-Mengelbier, L., Fredlund, E., Löfstedt, T., Noguera, R., Navarro, S., Nilsson, H., Pietras, A., Vallon-Christersson, J., Borg, Å., Gradin, K., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.08.026 · Cited by 735
Regulation of hypoxia-inducible factor-1α by NF-κB
van Uden, P., Kenneth, N. S., & Rocha, S. (2008) · Biochemical Journal · doi:10.1042/bj20080476 · Cited by 729
Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer
Wigerup, C., Påhlman, S., & Bexell, D. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.009 · Cited by 687
Interdependence of hypoxic and innate immune responses
Nizet, V., & Johnson, R. S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2607 · Cited by 708
Self-citationMarti, H. J. H., Bernaudin, M., Bellail, A., Schoch, H., Euler, M., Petit, E., & Risau, W. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64964-4 · Cited by 680
Hypoxia-inducible factors enhance the effector responses of CD8(+) T cells to persistent antigen
Doedens, A. L., Phan, A. T., Stradner, M. H., Fujimoto, J. K., Nguyen, J. V., Yang, E., Johnson, R. S., & Goldrath, A. W. (2013) · Nature Immunology · doi:10.1038/ni.2714 · Cited by 660
Self-citationHsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1α-degradative pathway
Isaacs, J. S., Jung, Y.-J., Mimnaugh, E. G., Martinez, A., Cuttitta, F., & Neckers, L. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204733200 · Cited by 663
Kim, J.-W., Gao, P., Liu, Y.-C., Semenza, G. L., & Dang, C. V. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00440-07 · Cited by 658
The Role of Hypoxia in Development of the Mammalian Embryo
Dunwoodie, S. L. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.11.008 · Cited by 651
Caniggia, I., Mostachfi, H., Winter, J., Gassmann, M., Lye, S. J., Kuliszewski, M., & Post, M. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8316 · Cited by 644
HIF-1 as a target for drug development
Giaccia, A., Siim, B. G., & Johnson, R. S. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1199 · Cited by 631
Self-citationSUMO-Specific Protease 1 Is Essential for Stabilization of HIF1α during Hypoxia
Cheng, J., Kang, X., Zhang, S., & Yeh, E. T. H. (2007) · Cell · doi:10.1016/j.cell.2007.08.045 · Cited by 624
Inhibition of HIF2α Is Sufficient to Suppress pVHL-Defective Tumor Growth
Kondo, K., Kim, W. Y., Lechpammer, M., & Kaelin, W. G. (2003) · PLoS Biology · doi:10.1371/journal.pbio.0000083 · Cited by 611
Passing the baton: the HIF switch
Koh, M. Y., & Powis, G. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.06.004 · Cited by 589
Hypoxia-inducible factor-2 (HIF-2) regulates hepatic erythropoietin in vivo
Rankin, E. B., Biju, M. P., Liu, Q., Unger, T. L., Rha, J., Johnson, R. S., Simon, M. C., Keith, B., & Haase, V. H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30117 · Cited by 596
Self-citationPhysiological and pathological responses to hypoxia
Michiels, C. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63747-9 · Cited by 559
Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis
Karhausen, J., Furuta, G. T., Tomaszewski, J. E., Johnson, R. S., Colgan, S. P., & Haase, V. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200421086 · Cited by 655
Self-citationTumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies
Shannon, A. M., Bouchier-Hayes, D. J., Condron, C. M., & Toomey, D. (2003) · Cancer Treatment Reviews · doi:10.1016/s0305-7372(03)00003-3 · Cited by 559
Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1
Semenza, G. L. (2007) · Biochemical Journal · doi:10.1042/bj20070389 · Cited by 541
Sonveaux, P., Copetti, T., De Saedeleer, C. J., Végran, F., Verrax, J., Kennedy, K. M., Moon, E. J., Dhup, S., Danhier, P., Frérart, F., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033418 · Cited by 536
The effect of HIF on metabolism and immunity
Taylor, C. T., & Scholz, C. C. (2022) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00587-8 · Cited by 517
Scortegagna, M., Ding, K., Oktay, Y., Gaur, A., Thurmond, F., Yan, L.-J., Marck, B. T., Matsumoto, A. M., Shelton, J. M., Richardson, J. A., et al. (2003) · Nature Genetics · doi:10.1038/ng1266 · Cited by 496
HIF-2α, but not HIF-1α, promotes iron absorption in mice
Mastrogiannaki, M., Matak, P., Keith, B., Simon, M. C., Vaulont, S., & Peyssonnaux, C. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38499 · Cited by 502
Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway
Kung, A. L., Zabludoff, S. D., France, D. S., Freedman, S. J., Tanner, E. A., Vieira, A., Cornell-Kennon, S., Lee, J., Wang, B., Wang, J., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.009 · Cited by 480
Acute postnatal ablation of Hif-2 α results in anemia
Gruber, M., Hu, C.-J., Johnson, R. S., Brown, E. J., Keith, B., & Simon, M. C. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608382104 · Cited by 457
Self-citationZhang, X., Zhou, K., Wang, R., Cui, J., Lipton, S. A., Liao, F.-F., Xu, H., & Zhang, Y.-W. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608856200 · Cited by 436
Lum, J. J., Bui, T., Gruber, M., Gordan, J. D., DeBerardinis, R. J., Covello, K. L., Simon, M. C., & Thompson, C. B. (2007) · Genes & Development · doi:10.1101/gad.1529107 · Cited by 429
The hypoxic response of tumors is dependent on their microenvironment
Blouw, B., Song, H., Tihan, T., Bosze, J., Ferrara, N., Gerber, H.-P., Johnson, R. S., & Bergers, G. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00194-6 · Cited by 408
Self-citationJögi, A., Øra, I., Nilsson, H., Lindeheim, Å., Makino, Y., Poellinger, L., Axelson, H., & Påhlman, S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.102660199 · Cited by 399
Mammalian Per-Arnt-Sim Proteins in Environmental Adaptation
McIntosh, B. E., Hogenesch, J. B., & Bradfield, C. A. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135922 · Cited by 352
Hypoxic regulation of erythropoiesis and iron metabolism
Haase, V. H. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00174.2010 · Cited by 347
Regulation of Metabolism by Hypoxia-Inducible Factor 1
Semenza, G. L. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010678 · Cited by 342
Liao, D., Corle, C., Seagroves, T. N., & Johnson, R. S. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2701 · Cited by 339
Self-citationThe hypoxia-inducible factor-1α is a negative factor for tumor therapy
Unruh, A., Ressel, A., Mohamed, H. G., Johnson, R. S., Nadrowitz, R., Richter, E., Katschinski, D. M., & Wenger, R. H. (2003) · Oncogene · doi:10.1038/sj.onc.1206385 · Cited by 334
Self-citationLahiri, S., Roy, A., Baby, S. M., Hoshi, T., Semenza, G. L., & Prabhakar, N. R. (2006) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2005.07.001 · Cited by 312
Hepatic HIF-2 regulates erythropoietic responses to hypoxia in renal anemia
Kapitsinou, P. P., Liu, Q., Unger, T. L., Rha, J., Davidoff, O., Keith, B., Epstein, J. A., Moores, S. L., Erickson-Miller, C. L., & Haase, V. H. (2010) · Blood · doi:10.1182/blood-2010-02-270322 · Cited by 307
miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target
Serocki, M., Bartoszewska, S., Janaszak-Jasiecka, A., Ochocka, R. J., Collawn, J. F., & Bartoszewski, R. (2018) · Angiogenesis · doi:10.1007/s10456-018-9600-2 · Cited by 288
Iron-regulatory proteins limit hypoxia-inducible factor-2α expression in iron deficiency
Sanchez, M., Galy, B., Muckenthaler, M. U., & Hentze, M. W. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1222 · Cited by 294
Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure
Minamishima, Y. A., Moslehi, J., Bardeesy, N., Cullen, D., Bronson, R. T., & Kaelin, W. G. (2008) · Blood · doi:10.1182/blood-2007-10-117812 · Cited by 294
Bakker, W. J., Harris, I. S., & Mak, T. W. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.10.035 · Cited by 277
Role of hypoxia-inducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency
Mukhopadhyay, C. K., Mazumder, B., & Fox, P. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000636200 · Cited by 274
Hypoxia inducible factor (HIF) function in innate immunity and infection
Zinkernagel, A. S., Johnson, R. S., & Nizet, V. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0282-2 · Cited by 265
Self-citationErythropoietin regulates tumour growth of human malignancies
Yasuda, Y. (2003) · Carcinogenesis · doi:10.1093/carcin/bgg060 · Cited by 257
Mitochondrial H2O2 Regulates the Angiogenic Phenotype via PTEN Oxidation
Connor, K. M., Subbaram, S., Regan, K. J., Nelson, K. K., Mazurkiewicz, J. E., Bartholomew, P. J., Aplin, A. E., Tai, Y.-T., Aguirre-Ghiso, J., Flores, S. C., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m410690200 · Cited by 251
Welsh, S., Williams, R., Kirkpatrick, L., Paine-Murrieta, G., & Powis, G. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.233.3.3 · Cited by 240
Inhibition of hypoxia-inducible factor is sufficient for growth suppression of VHL−/− tumors
Zimmer, M., Doucette, D., Siddiqui, N., & Iliopoulos, O. (2004) · Molecular Cancer Research · doi:10.1158/1541-7786.89.2.2 · Cited by 244
Hypoxia, HIF-1, and the Pathophysiologi of Common Human Diseases
Semenza, G. L., Agani, F., Feldser, D., Lyer, N., Kotch, L., Laughner, E., & Yu, 1. (2006) · Advances in Experimental Medicine and Biology · doi:10.1007/0-306-46825-5_12 · Cited by 241
The Effect of Hypoxia on Mesenchymal Stem Cell Biology
Ejtehadifar, M., Shamsasenjan, K., Movassaghpour, A., Akbarzadehlaleh, P., Dehdilani, N., Abbasi, P., Molaeipour, Z., & Saleh, M. (2015) · Advanced Pharmaceutical Bulletin · doi:10.15171/apb.2015.021 · Cited by 235
Takeda, K., Cowan, A., & Fong, G.-H. (2007) · Circulation · doi:10.1161/circulationaha.107.701516 · Cited by 236
Hypoxia-inducible factor-1α regulates β cell function in mouse and human islets
Cheng, K., Ho, K., Stokes, R., Scott, C., Lau, S. M., Hawthorne, W. J., O’Connell, P. J., Loudovaris, T., Kay, T. W., Kulkarni, R. N., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci35846 · Cited by 230
Kojima, H., Gu, H., Nomura, S., Caldwell, C. C., Kobata, T., Carmeliet, P., Semenza, G. L., & Sitkovsky, M. V. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052706699 · Cited by 224
Molecular pathways: hypoxia response in immune cells fighting or promoting cancer
Palazón, A., Aragonés, J., Morales-Kastresana, A., de Landázuri, M. O., & Melero, I. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1591 · Cited by 214
Lukashev, D., Klebanov, B., Kojima, H., Grinberg, A., Ohta, A., Berenfeld, L., Wenger, R. H., Ohta, A., & Sitkovsky, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.8.4962 · Cited by 208
Otto, D. M. E., Henderson, C. J., Carrie, D., Davey, M., Gundersen, T. E., Blomhoff, R., Adams, R. H., Tickle, C., & Wolf, C. R. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.17.6103-6116.2003 · Cited by 189
Yan, Q., Bartz, S., Mao, M., Li, L., & Kaelin, W. G. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01514-06 · Cited by 193
Oxygen-Regulated Gene Expression in Bovine Blastocysts1
Harvey, A. J., Kind, K. L., Pantaleon, M., Armstrong, D. T., & Thompson, J. G. (2004) · Biology of Reproduction · doi:10.1095/biolreprod.104.028639 · Cited by 189
From oxygen to erythropoietin: Relevance of hypoxia for retinal development, health and disease
Caprara, C., & Grimm, C. (2012) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2011.11.003 · Cited by 176
Multilineage embryonic hematopoiesis requires hypoxic ARNT activity
Adelman, D. M., Maltepe, E., & Simon, M. C. (1999) · Genes & Development · doi:10.1101/gad.13.19.2478 · Cited by 185
Endothelial Cell HIF-1α and HIF-2α Differentially Regulate Metastatic Success
Branco-Price, C., Zhang, N., Schnelle, M., Evans, C., Katschinski, D. M., Liao, D., Ellies, L., & Johnson, R. S. (2012) · Cancer Cell · doi:10.1016/j.ccr.2011.11.017 · Cited by 168
Self-citationJensen, R. L., Ragel, B. T., Whang, K., & Gillespie, D. (2006) · Journal of Neuro-Oncology · doi:10.1007/s11060-005-9103-z · Cited by 167
Kaelin, W. G. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010975 · Cited by 161
The TCA cycle and tumorigenesis: the examples of fumarate hydratase and succinate dehydrogenase
Pollard, P., Wortham, N., & Tomlinson, I. (2003) · Annals of Medicine · doi:10.1080/07853890310018458 · Cited by 159
The Pathogenesis of Adenomyosis vis-à-vis Endometriosis
Guo, S.-W. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9020485 · Cited by 165
“Hypoxia can also enhance cellular viability and proliferation through upregulation of insulin growth factor 2 (IGF-2) and IGF binding protein 3 (IGF-BP3) [85].”
Background
Metadata
- Authors
- Ryan, H. E., Lo, J., & Johnson, R. S.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Johnson, Randall S.
- Venue
- The EMBO Journal
- Published
- 1998-06-01
- Volume
- 17
- Issue
- 11
- Pages
- 3005-3015
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170640
- OpenAlex
- W2109492293
- Cited by
- 1,579
- References
- 6
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 27 · 2023: 28 · 2022: 38 · 2021: 37 · 2020: 40 · 2019: 31 · 2018: 38 · 2017: 35 · 2016: 40 · 2015: 53 · 2014: 58 · 2013: 71 · 2012: 57
- FWCI
- 22.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of California, San Diego
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Keywords
- HIF-1α, hypoxia-inducible factor, hypoxia, tumor angiogenesis, vascular endothelial growth factor, embryonic stem cells, somite development, oxygenation, ARNT
- MeSH terms
- Animals, DNA-Binding Proteins, Embryo, Mammalian, Gene Expression Regulation, Head, Male, Nervous System, Nuclear Proteins, Phosphoglycerate Kinase, Stem Cells, Transcription Factors, Yolk Sac, Cell Hypoxia, Up-Regulation, Apoptosis, Gene Deletion, Teratocarcinoma, Mice, Knockout, Mice, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
