Cited by 808Cancer, Hypoxia, and MetabolismAngiogenesis and VEGF in CancerErythropoietin and Anemia Treatment

The DOI matches its Crossref record; 105 of the 105 references it cites were found in a registry or an index.

The role of hypoxia-inducible factors in tumorigenesis

Open access

Rankin, E B, Giaccia, A J·2008·Cell Death & Differentiation

DOI 10.1038/cdd.2008.21PMC PMC3050610

Open this paper in CoChat — free account Open PDF

Abstract

Hypoxia-inducible factors (HIFs) are essential mediators of the cellular oxygen-signaling pathway. They are heterodimeric transcription factors consisting of an oxygen-sensitive alpha subunit (HIF-alpha) and a constitutive beta subunit (HIF-beta) that facilitate both oxygen delivery and adaptation to oxygen deprivation by regulating the expression of genes that control glucose uptake, metabolism, angiogenesis, erythropoiesis, cell proliferation, and apoptosis. In most experimental models, the HIF pathway is a positive regulator of tumor growth as its inhibition often results in tumor suppression. In clinical samples, HIF is found elevated and correlates with poor patient prognosis in a variety of cancers. In summary, HIF regulates multiple aspects of tumorigenesis, including angiogenesis, proliferation, metabolism, metastasis, differentiation, and response to radiation therapy, making it a critical regulator of the malignant phenotype.

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

Crossref · 10.1038/cdd.2008.21

Cites

105 of 105 references verified0 citation errors · 0 not checkable

Statistics

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

1 retracted

Lysyl oxidase is essential for hypoxia-induced metastasis
Erler, J. T., Bennewith, K. L., Nicolau, M., Dornhöfer, N., Kong, C., Le, Q.-T., Chi, J.-T. A., Jeffrey, S. S., & Giaccia, A. J. (2006) · Nature · doi:10.1038/nature04695 · Cited by 1,309
Self-citation
Retracted
The hallmarks of cancer
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673
On the origin of cancer cells
Warburg, O. (1956) · Science · doi:10.1126/science.123.3191.309 · Cited by 13,425
Stem cells, cancer, and cancer stem cells
Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001) · Nature · doi:10.1038/35102167 · Cited by 9,738
Angiogenesis in cancer and other diseases
Carmeliet, P., & Jain, R. K. (2000) · Nature · doi:10.1038/35025220 · Cited by 9,070
Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl Hydroxylation
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · cited 1×
“Hydroxylation of conserved proline residues within the HIF-a ODD by prolyl-4hydroxylase domain (PHD)-containing proteins mediates pVHL binding and degradation.(20,21) Under hypoxia, HIF-a subunits are stabilized and translocate to the nucleus, where they heterodimerize with ARNT and bind to HREs located within regulat…”
Background
Identification of the von Hippel-Lindau Disease Tumor Suppressor Gene
Latif, F., Tory, K., Gnarra, J. R., Yao, M., Duh, F.-M. C., Orcutt, M. L., Stackhouse, T. M., Kuzmin, I., Modi, W. S., Geil, L., et al. (1993) · Science · doi:10.1126/science.8493574 · Cited by 2,971
Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1
Ceradini, D. J., Kulkarni, A. R., Callaghan, M. J., Tepper, O. M., Bastidas, N., Kleinman, M. E., Capla, J. M., Galiano, R. D., Levine, J. P., & Gurtner, G. C. (2004) · Nature Medicine · doi:10.1038/nm1075 · Cited by 2,600
Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis
Carmeliet, P., Dor, Y., Herbert, J.-M., Fukumura, D., Brusselmans, K., Dewerchin, M., Neeman, M., Bono, F., Abramovitch, R., Maxwell, P., et al. (1998) · Nature · doi:10.1038/28867 · Cited by 2,502
Hypoxia in cancer: significance and impact on clinical outcome
Vaupel, P., & Mayer, A. (2007) · Cancer and Metastasis Reviews · doi:10.1007/s10555-007-9055-1 · Cited by 2,240
Regulation of hypoxia-inducible factor 1α is mediated by an O 2 -dependent degradation domain via the ubiquitin-proteasome pathway
Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113
Purification and Characterization of Hypoxia-inducible Factor 1
Wang, G. L., & Semenza, G. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.3.1230 · Cited by 2,094
Mitochondrial reactive oxygen species trigger hypoxia-induced transcription
Chandel, N. S., Maltepe, E., Goldwasser, E., Mathieu, C. E., Simon, M. C., & Schumacker, P. T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11715 · Cited by 1,926
Vascular Permeability Factor/Vascular Endothelial Growth Factor: A Critical Cytokine in Tumor Angiogenesis and a Potential Target for Diagnosis and Therapy
Dvorak, H. F. (2002) · Journal of Clinical Oncology · doi:10.1200/jco.2002.10.088 · Cited by 1,600
HIF‐1α is required for solid tumor formation and embryonic vascularization
Ryan, H. E., Lo, J., & Johnson, R. S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.11.3005 · Cited by 1,579
Asparagine 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
Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing
Guzy, R. D., Hoyos, B., Robin, E., Chen, H., Liu, L., Mansfield, K. D., Simon, M. C., Hammerling, U., & Schumacker, P. T. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.001 · Cited by 1,545
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
FIH-1: a novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity
Mahon, P. C., Hirota, K., & Semenza, G. L. (2001) · Genes & Development · doi:10.1101/gad.924501 · Cited by 1,385
Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells.
Tian, H., McKnight, S. L., & Russell, D. W. (1997) · Genes & Development · doi:10.1101/gad.11.1.72 · Cited by 1,351
The Expression and Distribution of the Hypoxia-Inducible Factors HIF-1α and HIF-2α in Normal Human Tissues, Cancers, and Tumor-Associated Macrophages
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
HIF-1 and mechanisms of hypoxia sensing
Semenza, G. L. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00194-0 · Cited by 1,301
Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension
Jiang, B. H., Semenza, G. L., Bauer, C., & Marti, H. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.4.c1172 · Cited by 1,213
Activation of Hypoxia-inducible Transcription Factor Depends Primarily upon Redox-sensitive Stabilization of Its α Subunit
Huang, E. L., Arany, Z. P., Livingston, D. M., & Bunn, H. F. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.32253 · Cited by 1,204
Regulation of Hypoxia-Inducible Factor 1α Expression and Function by the Mammalian Target of Rapamycin
Hudson, C. C., Liu, M., Chiang, G. G., Otterness, D. M., Loomis, D. C., Kaper, F., Giaccia, A. J., & Abraham, R. T. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.20.7004-7014.2002 · Cited by 1,186
Self-citation
Hypoxia requires Notch signaling to maintain the undifferentiated cell state
Gustafsson, M. V., Zheng, X., Pereira, T., Gradin, K., Jin, S., Lundkvist, J., Ruas, J. L., Poellinger, L., Lendahl, U., & Bondesson, M. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.09.010 · Cited by 1,109
A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1α regulates the VEGF expression and is potentially involved in lung and vascular development
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
Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors
Moeller, B. J., Cao, Y., Li, C. Y., & Dewhirst, M. W. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00115-1 · Cited by 996
mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways
Majumder, P. K., Febbo, P. G., Bikoff, R., Berger, R., Xue, Q., McMahon, L. M., Manola, J., Brugarolas, J., McDonnell, T. J., Golub, T. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1052 · Cited by 964
Cloning of a Factor Required for Activity of the Ah (Dioxin) Receptor
Hoffman, E. C., Reyes, H., Chu, F., Sander, F. C., Conley, L. H., Brooks, B. A., & Hankinson, O. (1991) · Science · doi:10.1126/science.1852076 · Cited by 958
Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma
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
Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein.
Iliopoulos, O., Levy, A. P., Jiang, C., Kaelin, W. G., & Goldberg, M. A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.20.10595 · Cited by 896
HIF-1 inhibits mitochondrial biogenesis and cellular respiration in VHL-deficient renal cell carcinoma by repression of C-MYC activity
Zhang, H., Gao, P., Fukuda, R., Kumar, G., Krishnamachary, B., Zeller, K. I., Dang, C. V., & Semenza, G. L. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.001 · Cited by 885
Chemokine receptor CXCR4 downregulated by von Hippel–Lindau tumour suppressor pVHL
Staller, P., Sulitkova, J., Lisztwan, J., Moch, H., Oakeley, E. J., & Krek, W. (2003) · Nature · doi:10.1038/nature01874 · Cited by 870
Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia
Parmar, K., Mauch, P., Vergilio, J.-A., Sackstein, R., & Down, J. D. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701152104 · Cited by 867
HIF-2α regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growthPreprint
Covello, K. L., Kehler, J., Yu, H., Gordan, J. D., Arsham, A. M., Hu, C., Labosky, P. A., Simon, M. C., & Keith, B. (2006) · Genes & Development · doi:10.1101/gad.1399906 · Cited by 850
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-citation
Low O 2 tensions and the prevention of differentiation of hES cells
Ezashi, T., Das, P., & Roberts, R. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501283102 · Cited by 824
HIF-2α Promotes Hypoxic Cell Proliferation by Enhancing c-Myc Transcriptional Activity
Gordan, J. D., Bertout, J. A., Hu, C.-J., Diehl, J. A., & Simon, M. C. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.02.006 · Cited by 781
Identification of the Ah Receptor Nuclear Translocator Protein (Arnt) as a Component of the DNA Binding Form of the Ah Receptor
Reyes, H., Reisz‐Porszasz, S., & Hankinson, O. (1992) · Science · doi:10.1126/science.256.5060.1193 · Cited by 777
Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia
Bruick, R. K. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.16.9082 · Cited by 767
Widespread, hypoxia‐inducible expression of HIF‐2α in distinct cell populations of different organs
Wiesener, M. S., Jürgensen, J. S., Rosenberger, C., Scholze, C. K., Hörstrup, J. H., Warnecke, C., Mandriota, S. J., Bechmann, I., Frei, U. A., Pugh, C. W., et al. (2002) · The FASEB Journal · doi:10.1096/fj.02-0445fje · Cited by 767
Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation
Brunelle, J. K., Bell, E. L., Quesada, N. M., Vercauteren, K., Tiranti, V., Zeviani, M., Scarpulla, R. C., & Chandel, N. S. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.002 · Cited by 763
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
Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression
Makino, Y., Cao, R., Svensson, K., Bertilsson, G., Asman, M., Tanaka, H., Cao, Y., Berkenstam, A., & Poellinger, L. (2001) · Nature · doi:10.1038/35107085 · Cited by 705
HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors.
Sowter, H., Ratcliffe, P. J., Watson, P. H., Greenberg, A. H., & Harris, A. L. (2001) · PubMed · Cited by 705
HIF-1α induces cell cycle arrest by functionally counteracting Myc
Koshiji, M., Kageyama, Y., Pete, E. A., Horikawa, I., Barrett, J. C., & Huang, L. E. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600196 · Cited by 652
Untitled work
(2000) · PubMed · Cited by 614
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
Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-α activation
Mansfield, K. D., Guzy, R. D., Pan, Y., Young, R. M., Cash, T. P., Schumacker, P. T., & Simon, M. C. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.003 · Cited by 606
Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha.
Gu, Y.-Z., Moran, S. M., Hogenesch, J. B., Wartman, L. D., & Bradfield, C. A. (1998) · Europe PMC (PubMed Central) · Cited by 577
Insulin induces transcription of target genes through the hypoxia‐inducible factor HIF‐1α/ARNT
Zelzer, E., Levy, Y., Kahana, C., Shilo, B., Rubinstein, M., & Cohen, B. (1998) · The EMBO Journal · doi:10.1093/emboj/17.17.5085 · Cited by 574
Untitled work
(2001) · PubMed · Cited by 557
TSC2 regulates VEGF through mTOR-dependent and -independent pathways
Brugarolas, J. B., Vazquez, F., Reddy, A., Sellers, W. R., & Kaelin, W. G. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00187-9 · Cited by 528
Activation of Hypoxia-inducible Factor-1; Definition of Regulatory Domains within the α Subunit
Pugh, C. W., O'Rourke, J. F., Nagao, M., Gleadle, J., & Ratcliffe, P. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.17.11205 · Cited by 526
c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription
Arabi, A., Wu, S., Ridderstråle, K., Bierhoff, H., Shiue, C.-N., Fátyol, K., Fahlén, S., Hydbring, P., Söderberg, O., Grummt, I., et al. (2005) · Nature Cell Biology · doi:10.1038/ncb1225 · Cited by 507
Induction of Vascular Endothelial Growth Factor by Hypoxia Is Modulated by a Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in Ha-ras-Transformed Cells Through a Hypoxia Inducible Factor-1 Transcriptional Element
Mazure, N. M., Chen, E. Y., Laderoute, K. R., & Giaccia, A. J. (1997) · Blood · doi:10.1182/blood.v90.9.3322 · Cited by 500
Self-citation
Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival
Giatromanolaki, A., Koukourakis, M. I., Sivridis, E., Turley, H., Talks, K., Pezzella, F., Gatter, K. C., & Harris, A. L. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.2018 · Cited by 478
Inhibition of PPARγ2 Gene Expression by the HIF-1-Regulated Gene DEC1/Stra13
Yun, Z., Maecker, H. L., Johnson, R. S., & Giaccia, A. J. (2002) · Developmental Cell · doi:10.1016/s1534-5807(02)00131-4 · Cited by 460
Self-citation
Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion
Zagzag, D., Lukyanov, Y., Lan, L., Ali, M., Esencay, M., Méndez, O., Yee, H. T., Voura, E. B., & Newcomb, E. W. (2006) · Laboratory Investigation · doi:10.1038/labinvest.3700482 · Cited by 408
Untitled work
(2002) · PubMed · Cited by 385
Hypoxia attenuates the expression of E-cadherin via up-regulation of SNAIL in ovarian carcinoma cells
Imai, T., Horiuchi, A., Wang, C., Oka, K., Ohira, S., Nikaido, T., & Konishi, I. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63501-8 · Cited by 377
Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity
Moeller, B. J., Dreher, M. R., Rabbani, Z. N., Schroeder, T., Cao, Y., Li, C. Y., & Dewhirst, M. W. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.06.016 · Cited by 374
HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1α and developmentally expressed in blood vessels
Flamme, I., Fröhlich, T., von Reutern, M., Kappel, A., Damert, A., & Risau, W. (1997) · Mechanisms of Development · doi:10.1016/s0925-4773(97)00674-6 · Cited by 373
BNIP3 Is an RB/E2F Target Gene Required for Hypoxia-Induced Autophagy
Tracy, K., Dibling, B. C., Spike, B. T., Knabb, J. R., Schumacker, P., & Macleod, K. F. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02246-06 · Cited by 369
The N-Terminal Transactivation Domain Confers Target Gene Specificity of Hypoxia-inducible Factors HIF-1α and HIF-2α
Hu, C.-J., Sataur, A., Wang, L., Chen, H., & Simon, M. C. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-05-0419 · Cited by 355
Epidermal Growth Factor and Hypoxia-induced Expression of CXC Chemokine Receptor 4 on Non-small Cell Lung Cancer Cells Is Regulated by the Phosphatidylinositol 3-Kinase/PTEN/AKT/Mammalian Target of Rapamycin Signaling Pathway and Activation of Hypoxia Inducible Factor-1α
Phillips, R. J., Mestas, J., Gharaee‐Kermani, M., Burdick, M. D., Sica, A., Belperio, J. A., Keane, M. P., & Strieter, R. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500963200 · Cited by 327
Coexpression of hypoxia-inducible factors 1alpha and 2alpha, carbonic anhydrase IX, and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival.
Hui, E. P., Chan, A. T. �., Pezzella, F., Turley, H., To, K., Poon, T. C. W., Zee, B. C.-Y., Mo, F. K. F., Teo, P. M. L., Huang, D. P., et al. (2002) · PubMed · Cited by 304
Determination of hypoxic region by hypoxia marker in developing mouse embryos in vivo: A possible signal for vessel development
Lee, Y. M., Jeong, C., Koo, S.-Y., Son, M. J., Song, H. S., Bae, S., Raleigh, J. A., Chung, H., Yoo, M., & Kim, K. (2001) · Developmental Dynamics · doi:10.1002/1097-0177(20010201)220:2 · Cited by 298
HIF-1 mediates the Warburg effect in clear cell renal carcinoma
Semenza, G. L. (2007) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-007-9081-2 · Cited by 281
Regulation of Angiogenesis by Hypoxia and Hypoxia‐Inducible Factors
Hickey, M. M., & Simon, M. C. (2006) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(06)76007-0 · Cited by 273
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)
Hirose, K., Morita, M., Ema, M., Mimura, J., Hamada, H., Fujii, H., Saijo, Y., Gotoh, O., Sogawa, K., & Fujii‐Kuriyama, Y. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.4.1706 · Cited by 271
Regulation of E-cadherin Expression by VHL and Hypoxia-Inducible Factor
Esteban, M. A., Tran, M. G. B., Harten, S. K., Hill, P., Castellanos, M. C., Chandra, A., Raval, R., O'Brien, T. S., & Maxwell, P. H. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2670 · Cited by 262
VHL Promotes E2 Box-Dependent E-Cadherin Transcription by HIF-Mediated Regulation of SIP1 and Snail
Evans, A. J., Russell, R. C., Roche, O., Burry, T. N., Fish, J. E., Chow, V. W. K., Kim, W. Y., Saravanan, A., Maynard, M. A., Gervais, M. L., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00892-06 · Cited by 255
The Transcriptional Activator Hypoxia Inducible Factor 2 (HIF-2/EPAS-1) Regulates the Oxygen-Dependent Expression of Erythropoietin in Cortical Astrocytes
Chavez, J. C., Baranova, O. V., Lin, J. C.-H., & Pichiule, P. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2838-06.2006 · Cited by 240
Hypoxia-Inducible Factor 1? Expression Correlates with Angiogenesis and Unfavorable Prognosis in Bladder Cancer
Theodoropoulos, V. (2004) · European Urology · doi:10.1016/j.eururo.2004.04.008 · Cited by 223
Hypoxia promotes a dedifferentiated phenotype in ductal breast carcinoma in situ.
Helczynska, K., Kronblad, Å., Jögi, A., Nilsson, E., Beckman, S., Landberg, G., & Påhlman, S. (2003) · PubMed · Cited by 200
Genetic evidence for a tumor suppressor role of HIF-2α
Acker, T., Díez‐Juan, A., Aragonés, J., Tjwa, M., Brusselmans, K., Moons, L., Fukumura, D., Moreno-Murciano, P., Herbert, J., Burger, A. M., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.07.003 · Cited by 187
Prognostic Impact of Hypoxia-Inducible Factors 1α and 2α in Colorectal Cancer Patients
Yoshimura, H., Dhar, D. K., Kohno, H., Kubota, H., Fujii, T., Ueda, S., Kinugasa, S., Tachibana, M., & Nagasue, N. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-0946-03 · Cited by 174
Expression of HIF-1α, CA IX, VEGF, and MMP-9 in surgically resected non-small cell lung cancer
Kim, S. J., Rabbani, Z. N., Dewhirst, M. W., Vujašković, Ž., Vollmer, R. T., Schreiber, E.-G., Oosterwijk, E., & Kelley, M. J. (2005) · Lung Cancer · doi:10.1016/j.lungcan.2005.03.036 · Cited by 167
Identification of Transactivation and Repression Functions of the Dioxin Receptor and Its Basic Helix-Loop-Helix/PAS Partner Factor Arnt: Inducible versus Constitutive Modes of Regulation
Whitelaw, M. L., Gustafsson, J.-Α., & Poellinger, L. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.12.8343 · Cited by 161
Loss of pVHL is sufficient to cause HIF dysregulation in primary cells but does not promote tumor growth
Mack, F. A., Rathmell, W. K., Arsham, A. M., Gnarra, J., Keith, B., & Simon, M. C. (2003) · Cancer Cell · doi:10.1016/s1535-6108(02)00240-4 · Cited by 160
Hypoxia-inducible factors 1?? and 2?? are related to vascular endothelial growth factor expression and a poorer prognosis in nodular malignant melanomas of the skin
Giatromanolaki, A. N., Sivridis, E., Kouskoukis, C., Gatter, K. C., Harris, A. L., & Koukourakis, M. I. (2003) · Melanoma Research · doi:10.1097/00008390-200310000-00008 · Cited by 155
Prognostic significance of HIF-1 alpha overexpression in human pancreatic cancer.
(2003) · PubMed · Cited by 138
VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells.
Bindra, R. S., Vasselli, J. R., Stearman, R. S., Linehan, W. M., & Klausner, R. D. (2002) · PubMed · Cited by 127
Targeted Replacement of Hypoxia-Inducible Factor-1α by a Hypoxia-Inducible Factor-2α Knock-in Allele Promotes Tumor Growth
Covello, K. L., Simon, M. C., & Keith, B. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3246 · Cited by 123
Nucleotide Sequence, Chromosomal Assignment and mRNA Expression of Mouse Hypoxia-Inducible Factor-1α
Wenger, R. H., Rolfs, A., Marti, H. H., Guénet, J., & Gassmann, M. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0845 · Cited by 122
Expression of hypoxia-inducible factor 1α, hypoxia-inducible factor 2α, and von Hippel–Lindau protein in epithelial ovarian neoplasms and allelic loss of von Hippel-Lindau gene: nuclear expression of hypoxia-inducible factor 1α is an independent prognostic factor in ovarian carcinoma
Osada, R., Horiuchi, A., Kikuchi, N., Yoshida, J., Hayashi, A., Ota, M., Katsuyama, Y., Mellilo, G., & Konishi, I. (2007) · Human Pathology · doi:10.1016/j.humpath.2007.02.010 · Cited by 120
Vhlh Gene Deletion Induces Hif-1-Mediated Cell Death in Thymocytes
Biju, M. P., Neumann, A. K., Bensinger, S. J., Johnson, R. S., Turka, L. A., & Haase, V. H. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.20.9038-9047.2004 · Cited by 111
The Role of ARNT2 in Tumor Angiogenesis and the Neural Response to Hypoxia
Maltepe, E., Keith, B., Arsham, A. M., Brorson, J. R., & Simon, M. C. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2928 · Cited by 108
Prognostic significance of HIF-2α/EPAS1 expression in hepatocellular carcinoma
Bangoura, G. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i23.3176 · Cited by 106
The relation between hypoxia‐inducible factor (HIF)‐1α and HIF‐2α expression with anemia and outcome in surgically treated head and neck cancer
Winter, S. C., SHAH, K. A., Han, C., Campo, L., Turley, H., Leek, R., Corbridge, R., Cox, G. J., & Harris, A. L. (2006) · Cancer · doi:10.1002/cncr.21983 · Cited by 94
Clinical Importance and Therapeutic Implications of the Pivotal CXCL12-CXCR4 (Chemokine Ligand-Receptor) Interaction in Cancer Cell Migration
Arya, M., Ahmed, H. U., Silhi, N., Williamson, M. P., & Patel, H. (2007) · Tumor Biology · doi:10.1159/000102979 · Cited by 84
Overexpression of Hypoxia-Inducible Factor-1α in Human Osteosarcoma: Correlation with Clinicopathological Parameters and Survival Outcome
Yang, Q., Zeng, B., Dong, Y., Shi, Z., Jiang, Z.-M., & Huang, J. (2007) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyl137 · Cited by 75
Radiation and inhibition of angiogenesis by canstatin synergize to induce HIF-1α–mediated tumor apoptotic switch
Magnon, C., Opolon, P., Ricard, M., Connault, E., Ardouin, P., Galaup, A., Métivier, D., Bidart, J., Germain, S., Perricaudet, M., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30269 · Cited by 65
Hypoxia-induced dedifferentiation in neuroblastoma cells
Jögi, A., Øra, I., Nilsson, H., Poellinger, L., Axelson, H., & Påhlman, S. (2003) · Cancer Letters · doi:10.1016/s0304-3835(03)00095-8 · Cited by 46
Molecular Genetics of Sporadic and Familial Renal Cell Carcinoma
Linehan, W. M. (2000) · doi:10.1007/978-1-4613-1101-0_3 · Cited by 44
Protocol of radiotherapy for glioblastoma according to the expression of HIF-1
Irie, N., Matsuo, T., & Nagata, I. (2004) · Brain Tumor Pathology · doi:10.1007/bf02482169 · Cited by 40
MOLECULAR GENETIC STUDIES OF SPORADIC AND FAMILIAL RENAL CELL CARCINOMA
Gnarra, J. R., Glenn, G. M., Latif, F., Anglard, P., Lerman, M. I., Zbar, B., & Linehan, W. M. (1993) · Urologic Clinics of North America · doi:10.1016/s0094-0143(21)00481-x · Cited by 40
Protection of HIF-1-deficient primary renal tubular epithelial cells from hypoxia-induced cell death is glucose dependent
Biju, M. P., Akai, Y., Shrimanker, N., & Haase, V. H. (2005) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00233.2005 · Cited by 35
Characteristic Chromosomal Aberrations in Sporadic Cerebellar Hemangioblastomas Revealed by Comparative Genomic Hybridization
Sprenger, S. H. E., Gijtenbeek, J. M. M., Wesseling, P., Sciot, R., Calenbergh, F. V., Lammens, M. M. Y., & Jeuken, J. W. M. (2001) · Journal of Neuro-Oncology · doi:10.1023/a:1010623119469 · Cited by 32
Relationship of hypoxia-inducible factor 1α and p21WAF1/CIP1 expression to cell apoptosis and clinical outcome in patients with gastric cancer
Mizokami, K., Kakeji, Y., Oda, S., & Maehara, Y. (2006) · World Journal of Surgical Oncology · doi:10.1186/1477-7819-4-94 · Cited by 24

Flagged first, then by citations

Sorted by citations

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
Hypoxic control of metastasis
Rankin, E. B., & Giaccia, A. J. (2016) · Science · doi:10.1126/science.aaf4405 · Cited by 1,340
Self-citation
Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response
McKeown, S. R. (2014) · The British Journal of Radiology · doi:10.1259/bjr.20130676 · Cited by 1,050
Oxidative Stress and Oxidative Damage in Carcinogenesis
Klaunig, J. E., Kamendulis, L. M., & Hocevar, B. A. (2009) · Toxicologic Pathology · doi:10.1177/0192623309356453 · Cited by 990
“2006) as well as hypoxia-inducible transcription factor 1 a (HIF-1a; Rankin and Giaccia 2008).”
BackgroundMethod
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

See all 808

Authors: Rankin, E. B., & Giaccia, A. J.
Affiliations: Stanford Medicine (US)
Corresponding author: Giaccia, A J
ORCID: Rankin, E B
Giaccia, A J
Venue: Cell Death & Differentiation
Publisher: Springer Science and Business Media LLC
Published: 2008-02-15
Volume: 15
Issue: 4
Pages: 678-685
ISSN: 1350-9047 (ISSN-L)
1476-5403
DOI: 10.1038/cdd.2008.21
PMC: PMC3050610
OpenAlex: W2014245338
Cited by: 806
References: 105
Citations by year: 2026: 18 · 2025: 24 · 2024: 30 · 2023: 34 · 2022: 43 · 2021: 42 · 2020: 39 · 2019: 38 · 2018: 33 · 2017: 44 · 2016: 45 · 2015: 48 · 2014: 56 · 2013: 51 · 2012: 46
FWCI: 5.10
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Cell Death and Differentiation (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (P01CA067166, T32CA009151)
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
Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
Keywords: hypoxia-inducible factor, carcinogenesis, oxygen signaling, hypoxia-inducible factor alpha, angiogenesis, cancer metabolism, tumor growth, metastasis, radiation response, tumor differentiation, prognosis, apoptosis, cell proliferation
MeSH terms: Endothelial PAS Domain-Containing Protein 1, Adaptation, Physiological, Animals, Hypoxia, Cell Differentiation, Energy Metabolism, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms, Neovascularization, Pathologic, Oxygen, Signal Transduction, Cell Hypoxia, Cell Proliferation, Basic Helix-Loop-Helix Proteins, 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

The role of hypoxia-inducible factors in tumorigenesis

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks