Hypoxia signalling in cancer and approaches to enforce tumour regression

The biology of VEGF and its receptors

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Targeting HIF-1 for cancer therapy

Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717

Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl Hydroxylation

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Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene

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Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis

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C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation

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VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia

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AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism

Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799

Angiogenesis as a therapeutic target

Ferrara, N., & Kerbel, R. S. (2005) · Nature · doi:10.1038/nature04483 · Cited by 2,653

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

Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis

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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

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

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

The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress

Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797

Epithelial–mesenchymal transitions in development and pathologies

Thiery, J. P. (2003) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2003.10.006 · Cited by 1,710

The role of autophagy in cancer development and response to therapy

Kondo, Y., Kanzawa, T., Sawaya, R. A., & Kondo, S. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1692 · Cited by 1,672

FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor

Lando, D., Peet, D. J., Gorman, J. J., Whelan, D. A., Whitelaw, M. L., & Bruick, R. K. (2002) · Genes & Development · doi:10.1101/gad.991402 · Cited by 1,550 · cited 1×

Growth factor regulation of autophagy and cell survival in the absence of apoptosis

Lum, J. J., Bauer, D. E., Kong, M., Harris, M. H., Li, C., Lindsten, T., & Thompson, C. B. (2005) · Cell · doi:10.1016/j.cell.2004.11.046 · Cited by 1,487

Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex

Brugarolas, J., Lei, K., Hurley, R. L., Manning, B. D., Reiling, J. H., Hafen, E., Witters, L. A., Ellisen, L. W., & Kaelin, W. G. (2004) · Genes & Development · doi:10.1101/gad.1256804 · Cited by 1,384

Amino Acid Sufficiency and mTOR Regulate p70 S6 Kinase and eIF-4E BP1 through a Common Effector Mechanism

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HIF prolyl‐hydroxylase 2 is the key oxygen sensor setting low steady‐state levels of HIF‐1α in normoxia

Berra, E., Benizri, E., Ginouvès, A., Volmat, V., Roux, D., & Pouysségur, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg392 · Cited by 1,348

Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene

Pennacchietti, S., Michieli, P., Galluzzo, M., Mazzone, M., Giordano, S., & Comoglio, P. M. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00085-0 · Cited by 1,311

Mechanisms and consequences of activation of protein kinase B/Akt

Downward, J. (1998) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(98)80149-x · Cited by 1,304

Phosphorylation and Functional Inactivation of TSC2 by Erk

Ma, L., Chen, Z., Erdjument-Bromage, H., Tempst, P., & Pandolfi, P. P. (2005) · Cell · doi:10.1016/j.cell.2005.02.031 · Cited by 1,268

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

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

Tuberous Sclerosis Complex Gene Products, Tuberin and Hamartin, Control mTOR Signaling by Acting as a GTPase-Activating Protein Complex toward Rheb

Tee, A. R., Manning, B. D., Roux, P. P., Cantley, L. C., & Blenis, J. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00506-2 · Cited by 1,080

The SLC16 gene family?from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond

Halestrap, A. P., & Meredith, D. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1067-2 · Cited by 1,047

Mitogen-activated protein kinases p42mapk and p44mapk are required for fibroblast proliferation.

Pagès, G., Lenormand, P., L’Allemain, G., Chambard, J., Meloche, S., & Pouysségur, J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.18.8319 · Cited by 984

HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: Novel role of fumarate in regulation of HIF stability

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

Role of VHL Gene Mutation in Human Cancer

Kim, W. Y., & Kaelin, W. G. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.05.061 · Cited by 953

Hydroxylation of HIF-1: Oxygen Sensing at the Molecular Level

Semenza, G. L. (2004) · Physiology · doi:10.1152/physiol.00001.2004 · Cited by 923

The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis

Cardone, R. A., Casavola, V., & Reshkin, S. J. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1713 · Cited by 897

The Plasma Membrane Lactate Transporter MCT4, but Not MCT1, Is Up-regulated by Hypoxia through a HIF-1α-dependent Mechanism

Ullah, M. S., Davies, A. J., & Halestrap, A. P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511397200 · Cited by 894

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

The Role of Hypoxia-Induced Factors in Tumor Progression

Vaupel, P. W. (2004) · The Oncologist · doi:10.1634/theoncologist.9-90005-10 · Cited by 851

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

Insulin-like Growth Factor 1 Induces Hypoxia-inducible Factor 1-mediated Vascular Endothelial Growth Factor Expression, Which is Dependent on MAP Kinase and Phosphatidylinositol 3-Kinase Signaling in Colon Cancer Cells

Fukuda, R., Hirota, K., Fan, F., Jung, Y. D., Ellis, L. M., & Semenza, G. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203781200 · Cited by 830

p42/p44 Mitogen-activated Protein Kinases Phosphorylate Hypoxia-inducible Factor 1α (HIF-1α) and Enhance the Transcriptional Activity of HIF-1

Richard, D. E., Berra, E., Gothié, E., Roux, D., & Pouysségur, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.46.32631 · Cited by 797

Molecular cloning, primary structure, and expression of the human growth factor-activatable antiporter

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Autophagy in metazoans: cell survival in the land of plenty

Lum, J. J., DeBerardinis, R. J., & Thompson, C. B. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1660 · Cited by 774

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

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

Regulation of the Hypoxia-inducible Transcription Factor 1α by the Ubiquitin-Proteasome Pathway

Kallio, P. J., Wilson, W. J., O’Brien, S. L., Makino, Y., & Poellinger, L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6519 · Cited by 754

The Tie-2 ligand Angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies

Fiedler, U., Scharpfenecker, M., Koidl, S., Hegen, A., Grunow, V., Schmidt, J. M., Kriz, W., Thurston, G., & Augustin, H. G. (2004) · Blood · doi:10.1182/blood-2003-10-3685 · Cited by 742

Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wallPreprint

Lindblom, P., Gerhardt, H., Liebner, S., Abramsson, A., Enge, M., Hellström, M., Bäckström, G., Fredriksson, S., Landegren, U. D., Nyström, H. C., et al. (2003) · Genes & Development · doi:10.1101/gad.266803 · Cited by 674

Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer

Thomas, G. V., Tran, C., Mellinghoff, I. K., Welsbie, D. S., Chan, E., Fueger, B., Czernin, J., & Sawyers, C. L. (2006) · Nature Medicine · doi:10.1038/nm1337 · Cited by 604

Hypoxia-induced Transcriptional Activation and Increased mRNA Stability of Vascular Endothelial Growth Factor in C6 Glioma Cells

Ikeda, E., Achen, M. G., Breier, G., & Risau, W. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.34.19761 · Cited by 590

An expanding role for mTOR in cancer

Guertin, D. A., & Sabatini, D. M. (2005) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2005.06.007 · Cited by 522

Blood vessels and nerves: common signals, pathways and diseases

Carmeliet, P. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1158 · Cited by 513

Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity.

Kong, D., Park, E. J., Stephen, A. G., Calvani, M., Cardellina, J. H., Monks, A., Fisher, R. J., Shoemaker, R. H., & Melillo, G. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1235 · Cited by 508

Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2

Oliner, J. D., Min, H., Leal, J., Yu, D., Rao, S., You, E., Xiu, T., Kim, H. J., MEYER, S. R., Han, S. J., et al. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.09.030 · Cited by 471

Hypoxia-responsive transcription factors

Cummins, E. P., & Taylor, C. T. (2005) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-005-1413-7 · Cited by 469

Transcriptional regulation of the Vascular Endothelial Growth Factor gene?a concert of activating factors

Pagès, G., & Pouysségur, J. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.09.032 · Cited by 456

The SLC4 family of HCO3 ? transporters

Romero, M. F., Fulton, C. M., & Boron, W. F. (2004) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1180-2 · Cited by 454

Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases

Koivunen, P., Hirsilä, M., Günzler, V., Kivirikko, K. I., & Myllyharju, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312254200 · Cited by 447

A molecular role for lysyl oxidase‐like 2 enzyme in Snail regulation and tumor progression

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Activation of the HIF pathway in cancer

Maxwell, P. H. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00193-3 · Cited by 430

Hypoxia-Inducible Factor-1-Dependent Repression of E-cadherin in von Hippel-Lindau Tumor Suppressor–Null Renal Cell Carcinoma Mediated by TCF3, ZFHX1A, and ZFHX1B

Krishnamachary, B., Zagzag, D., Nagasawa, H., Rainey, K., Okuyama, H., Baek, J. H., & Semenza, G. L. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3719 · Cited by 415

The Immunosuppressant Rapamycin Mimics a Starvation-Like Signal Distinct from Amino Acid and Glucose Deprivation

Peng, T., Golub, T. R., & Sabatini, D. M. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.15.5575-5584.2002 · Cited by 404

Regulation of Angiopoietin-2 mRNA Levels in Bovine Microvascular Endothelial Cells by Cytokines and Hypoxia

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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

The Expanding Family of Eucaryotic Na+/H+Exchangers

Counillon, L., & Pouysségur, J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.1 · Cited by 371

Hypoxia-Inducible Factor-1-Dependent Repression of E-cadherin in von Hippel-Lindau Tumor Suppressor—Null Renal Cell Carcinoma Mediated by TCF3, ZFHX1A, and ZFHX1B

Gordon, M. S. (2007) · Yearbook of Oncology · doi:10.1016/s1040-1741(08)70352-x · Cited by 346

A molecular role for lysyl oxidase in breast cancer invasion.

Kirschmann, D. A., Seftor, E. A., Fong, S. F. T., Nieva, D. R. C., Sullivan, C. M., Edwards, E. M., Sommer, P., Csiszar, K., & Hendrix, M. J. C. (2002) · PubMed · Cited by 332

Hypoxia-inducible Factor-1α mRNA Contains an Internal Ribosome Entry Site That Allows Efficient Translation during Normoxia and Hypoxia

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Investigating hypoxic tumor physiology through gene expression patterns

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Two Independent Internal Ribosome Entry Sites Are Involved in Translation Initiation of Vascular Endothelial Growth Factor mRNA

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The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in DrosophilaPreprint

Reiling, J. H., & Hafen, E. (2004) · Genes & Development · doi:10.1101/gad.322704 · Cited by 306

The Oxygen Sensor Factor-Inhibiting Hypoxia-Inducible Factor-1 Controls Expression of Distinct Genes through the Bifunctional Transcriptional Character of Hypoxia-Inducible Factor-1α

Dayan, F., Roux, D., Brahimi-Horn, M. C., Pouyssegur, J., & Mazure, N. M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4564 · Cited by 294

Identification of Two Sp1 Phosphorylation Sites for p42/p44 Mitogen-activated Protein Kinases

Milanini, J., Pouysségur, J., & Pagès, G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201753200 · Cited by 291

Hypoxia Inducible Carbonic Anhydrase IX, Marker of Tumour: Hypoxia, Survival Pathway and Therapy Target

Potter, C. T., & Harris, A. L. (2004) · Cell Cycle · doi:10.4161/cc.3.2.618 · Cited by 279

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

New roles for the LKB1→AMPK pathway

Hardie, D. G. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.01.006 · Cited by 256

Monocarboxylate transporter MCT1 is a target for immunosuppression

Murray, C. M., Hutchinson, R., Bantick, J. R., Belfield, G., Benjamin, A., Brazma, D., Bundick, R. V., Cook, I. D., Craggs, R. I., Edwards, S., et al. (2005) · Nature Chemical Biology · doi:10.1038/nchembio744 · Cited by 253

Ras GTPases: integrins' friends or foes?

Kinbara, K., Goldfinger, L. E., Hansen, M. B., Chou, F.-L., & Ginsberg, M. H. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1229 · Cited by 238

Oncogenes and tumor angiogenesis: differential modes of vascular endothelial growth factor up-regulation in ras-transformed epithelial cells and fibroblasts.

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Silencing of the Hypoxia-Inducible Cell Death Protein BNIP3 in Pancreatic Cancer

Okami, J., Simeone, D. M., & Logsdon, C. D. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0089 · Cited by 237

MAP Kinases and Hypoxia in the Control of VEGF Expression

Berra, E., Pagès, G., & Pouysségur, J. (2000) · Cancer and Metastasis Reviews · doi:10.1023/a:1026506011458 · Cited by 222

Signalling via the hypoxia-inducible factor-1α requires multiple posttranslational modifications

Brahimi‐Horn, C., Mazure, N. M., & Pouysségur, J. (2004) · Cellular Signalling · doi:10.1016/j.cellsig.2004.04.010 · Cited by 222

Notch Activation Induces Endothelial Cell Cycle Arrest and Participates in Contact Inhibition: Role of p21 Cip1 Repression

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The hypoxia‐inducible‐factor hydroxylases bring fresh air into hypoxia signalling

Berra, E., Ginouvès, A., & Pouysségur, J. (2006) · EMBO Reports · doi:10.1038/sj.embor.7400598 · Cited by 205

Studies with glycolysis-deficient cells suggest that production of lactic acid is not the only cause of tumor acidity.

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Stress-activated protein kinases (JNK and p38/HOG) are essential for vascular endothelial growth factor mRNA stability

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Fidelity and spatio‐temporal control in MAP kinase (ERKs) signalling

Pouysségur, J., & Lenormand, P. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03707.x · Cited by 171

Dysregulation of HIF and VEGF is a unifying feature of the familial hamartoma syndromes

Brugarolas, J., & Kaelin, W. G. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.06.020 · Cited by 165

How do small GTPase signal transduction pathways regulate cell cycle entry?

Marshall, C. (1999) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)00044-7 · Cited by 161

HIF‐1‐dependent transcriptional activity is required for oxygen‐mediated HIF‐1α degradation

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The Pro-regions of Lysyl Oxidase and Lysyl Oxidase-like 1 Are Required for Deposition onto Elastic Fibers

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The von Hippel-Lindau gene, kidney cancer, and oxygen sensing.

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Expression of Angiopoietin-2 in Endothelial Cells Is Controlled by Positive and Negative Regulatory Promoter Elements

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Hypoxia-inducible factors and hypoxic cell death in tumour physiology

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