The DOI matches its Crossref record; 197 of the 197 references it cites were found in a registry or an index.
HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Open accessAbstract
Hypoxia-inducible factors (HIFs) are broadly expressed in human cancers, and HIF1α and HIF2α were previously suspected to promote tumour progression through largely overlapping functions. However, this relatively simple model has now been challenged in light of recent data from various approaches that reveal unique and sometimes opposing activities of these HIFα isoforms in both normal physiology and disease. These effects are mediated in part through the regulation of unique target genes, as well as through direct and indirect interactions with important oncoproteins and tumour suppressors, including MYC and p53. As HIF inhibitors are currently undergoing clinical evaluation as cancer therapeutics, a more thorough understanding of the unique roles performed by HIF1α and HIF2α in human neoplasia is warranted.
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 source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“By recruiting transcriptional co-activators, HIFs regulate the expression of numerous genes involved in different processes including angiogenesis, metabolism, erythropoiesis, apoptosis, pH regulation, metastasis, and cellular differentiation (Semenza, 2003;Keith et al., 2012).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Keith et al., 2012
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Deacetylation of HIF-2α by SIRT1, a deacetylase, increases HIF-2α's transcriptional activity, while deacetylation of HIF-1α results in transcriptional repression.”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Keith et al., 2012
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Interestingly, the expression of VEGF, which is commonly considered a HIF-1α and HIF-2α target gene [19], was unchanged in all of the samples examined.”
From Pilot trial of EZN-2968, an antisense oligonucleotide inhibitor of hypoxia-inducible factor-1 alpha (HIF-1α), in patients with refractory solid tumors (2014) · cites this paper as [19]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“GLUT-1, known to be targeted by both HIF-1α and HIF-2α, was only decreased in 2 patients [19].”
From Pilot trial of EZN-2968, an antisense oligonucleotide inhibitor of hypoxia-inducible factor-1 alpha (HIF-1α), in patients with refractory solid tumors (2014) · cites this paper as [19]
Experimental — accuracy not yet measured
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
1 retracted
RETRACTED: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization
Lee, K., Zhang, H., Qian, D. Z., Rey, S., Liu, J. O., & Semenza, G. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909353106 · Cited by 451
RetractedTargeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
Wang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5510 · Cited by 6,212
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
Blinded by the Light: The Growing Complexity of p53
Vousden, K. H., & Prives, C. (2009) · Cell · doi:10.1016/j.cell.2009.04.037 · Cited by 3,163
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
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380
Self-citationDefining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics
Semenza, G. L. (2010) · Oncogene · doi:10.1038/onc.2009.441 · Cited by 1,712
Hypoxia signalling in cancer and approaches to enforce tumour regression
Pouysségur, J., Dayan, F., & Mazure, N. M. (2006) · Nature · doi:10.1038/nature04871 · Cited by 1,676
Flagged first, then by citations
Cited by
Sorted by citations
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S. N., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,836
Broadening horizons: the role of ferroptosis in cancer
Chen, X., Kang, R., Kroemer, G., & Tang, D. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-00462-0 · Cited by 3,012
From Krebs to clinic: glutamine metabolism to cancer therapy
Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119
“BPTES inhibition of hGA(124-551), a truncated form of human kidneytype glutaminase.”
Iron and cancer: more ore to be mined
Torti, S. V., & Torti, F. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3495 · Cited by 1,621
Antiangiogenesis Strategies Revisited: From Starving Tumors to Alleviating Hypoxia
Jain, R. K. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.10.006 · Cited by 1,589
“…a protumorigenic and immunosuppressive phenotype (Casazza et al., 2014; Colegio et al., 2014; Finger and Giaccia, 2010; Hanahan and Coussens, 2012; Keith et al., 2012; Motz and Coukos, 2013; Noy and Pollard, 2014; Cancer Cell 26, November 10, 2014 ª2014 Elsevier Inc. 605 NS, not significant;…”
Hypoxia and the extracellular matrix: drivers of tumour metastasis
Gilkes, D. M., Semenza, G. L., & Wirtz, D. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3726 · Cited by 1,520
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations
Semenza, G. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67230 · Cited by 1,335
Normalizing Tumor Microenvironment to Treat Cancer: Bench to Bedside to Biomarkers
Jain, R. K. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.46.3653 · Cited by 1,248
Cellular Adaptation to Hypoxia through Hypoxia Inducible Factors and beyond
Lee, P., Chandel, N. S., & Simon, M. C. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0227-y · Cited by 1,272
Self-citationHIF transcription factors, inflammation, and immunity
Palazon, A., Goldrath, A. W., Nizet, V., & Johnson, R. S. (2014) · Immunity · doi:10.1016/j.immuni.2014.09.008 · Cited by 1,195
“As has been shown in cancer cells (Holmquist-Mengelbier et al., 2006; Keith et al., 2012; Warnecke et al., 2008), differing expression patterns of the HIF-1a and HIF-2a isoforms in immune cells depend on both intrinsic and extrinsic factors, and their resulting balance specifically contributes to…”
BackgroundSelf-citationAnoikis molecular pathways and its role in cancer progression
Paoli, P., Giannoni, E., & Chiarugi, P. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.026 · Cited by 1,160
Links between metabolism and cancerPreprint
Dang, C. V. (2012) · Genes & Development · doi:10.1101/gad.189365.112 · Cited by 1,021
AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo
Faubert, B., Boily, G., Izreig, S., Griss, T., Samborska, B., Dong, Z., Dupuy, F., Chambers, C., Fuerth, B. J., Viollet, B., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.001 · Cited by 949
“Several of the enzymes elevated in AMPKa-deficient cells are known targets of the transcription factor HIF-1a, one of the central regulators of glycolysis induced by hypoxia (Keith et al., 2012; Semenza, 2011).”
BackgroundVHL, the story of a tumour suppressor gene
Gossage, L., Eisen, T. G., & Maher, E. R. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3844 · Cited by 800
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
“A comprehensive description of HIF-α regulation and the conflicting roles of HIF-1α and HIF-2α are given in Keith et al. (2012).”
BackgroundInfluentialTargeting renal cell carcinoma with a HIF-2 antagonist
Chen, W., Hill, H., Christie, A., Kim, M. S., Holloman, E., Pavia-Jimenez, A., Homayoun, F., Ma, Y., Patel, N., Yell, P., et al. (2016) · Nature · doi:10.1038/nature19796 · Cited by 709
Regulation of mTORC1 and its impact on gene expression at a glance
Laplante, M., & Sabatini, D. M. (2013) · Journal of Cell Science · doi:10.1242/jcs.125773 · Cited by 697
“The increase in HIF1a activity, which results from oncogenic activation and/or intratumoral hypoxia, has been associated with an increased patient mortality in several types of cancer (reviewed by Keith et al., 2012).”
BackgroundThe histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
Sebastián, C., Zwaans, B. M. M., Silberman, D. M., Gymrek, M., Goren, A., Zhong, L., Ram, O., Truelove, J., Guimaraes, A. R., Toiber, D., et al. (2012) · Cell · doi:10.1016/j.cell.2012.10.047 · Cited by 660
“Moreover, HIF-1 α and HIF-2 α have overlapping functions, and how these two factors influence tumorigenesis remains still highly controversial (Keith et al., 2012).”
Monocarboxylate transporters in cancer
Payen, V. L., Mina, E., Hée, V. F. V., Porporato, P. E., & Sonveaux, P. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.07.006 · Cited by 688
Clear cell renal cell carcinoma ontogeny and mechanisms of lethality
Jonasch, E. W., Walker, C. L., & Rathmell, W. K. (2020) · Nature Reviews Nephrology · doi:10.1038/s41581-020-00359-2 · Cited by 667
How the Warburg effect supports aggressiveness and drug resistance of cancer cells?
Icard, P., Shulman, S. D., Farhat, D., Steyaert, J., Alifano, M., & Lincet, H. (2018) · Drug Resistance Updates · doi:10.1016/j.drup.2018.03.001 · Cited by 664
mTORC1 signaling and the metabolic control of cell growth
Ben‐Sahra, I., & Manning, B. D. (2017) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2017.02.012 · Cited by 668
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
Lee, Y. S., Kim, J.-W., Osborne, O., Oh, D. Y., Sasik, R., Schenk, S., Chen, A., Chung, H., Murphy, A., Watkins, S. M., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.012 · Cited by 598
Self-citationGlycolytic Reprogramming in Myofibroblast Differentiation and Lung Fibrosis
Xie, N., Tan, Z., Banerjee, S., Cui, H., Ge, J., Liu, R.-M., Bernard, K., Thannickal, V. J., & Liu, G. (2015) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201504-0780oc · Cited by 582
HIF ‐1 at the crossroads of hypoxia, inflammation, and cancer
Balamurugan, K. (2015) · International Journal of Cancer · doi:10.1002/ijc.29519 · Cited by 588
PDK1-Dependent Metabolic Reprogramming Dictates Metastatic Potential in Breast Cancer
Dupuy, F., Tabariès, S., Andrzejewski, S., Dong, Z., Blagih, J., Annis, M. G., Omeroglu, A., Gao, D., Leung, S., Amir, E., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.08.007 · Cited by 558
“HIF-1a Mediates Metabolic Reprogramming of Liver-Metastatic Breast Cancer Cells HIF-1a is a master transcription factor that controls metabolic reprogramming under low-O2 conditions, and it functions as a key regulator of glycolysis (Keith et al., 2012; Semenza, 2013).”
Tumor Microenvironment Complexity: Emerging Roles in Cancer Therapy
Swartz, M. A., Iida, N., Roberts, E. W., Sangaletti, S., Wong, M. H., Yull, F. E., Coussens, L. M., & DeClerck, Y. A. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0122 · Cited by 542
Fructose-1,6-bisphosphatase opposes renal carcinoma progression
Li, B., Qiu, B., Lee, D. S. M., Walton, Z. E., Ochocki, J. D., Mathew, L. K., Mancuso, A., Gade, T. P. F., Keith, B., Nissim, I., et al. (2014) · Nature · doi:10.1038/nature13557 · Cited by 535
Self-citationClinical implications of intratumor heterogeneity: challenges and opportunities
y Cajal, S. R., Sesé, M., Capdevila, C., Aasen, T., Mattos‐Arruda, L. D., Díaz‐Cano, S. J., Hernández‐Losa, J., & Castellví, J. (2020) · Journal of Molecular Medicine · doi:10.1007/s00109-020-01874-2 · Cited by 549
ROS production by mitochondria: function or dysfunction?
Palma, F. R., Gantner, B. N., Sakiyama, M. J., Filho, C. K. C., Shukla, S., Lacchini, R., Cunniff, B., & Bonini, M. G. (2023) · Oncogene · doi:10.1038/s41388-023-02907-z · Cited by 550
Hypoxia-Modified Cancer Cell Metabolism
Tameemi, W. A., Dale, T. P., Al-Jumaily, R. M. K., & Forsyth, N. R. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00004 · Cited by 524
Mitochondrial Dysfunction in Cancer
Boland, M. L., Chourasia, A. H., & Macleod, K. F. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00292 · Cited by 521
Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity
Dahia, P. L. M. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3648 · Cited by 545
Tumor Microenvironment in Pancreatic Cancer Pathogenesis and Therapeutic Resistance
Sherman, M. H., & Beatty, G. L. (2022) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-031621-024600 · Cited by 501
Metabolic checkpoints in activated T cells
Wang, R., & Green, D. R. (2012) · Nature Immunology · doi:10.1038/ni.2386 · Cited by 477
The nuclear factor kappa B signaling pathway: integrating metabolism with inflammation
Tornatore, L., Thotakura, A. K., Bennett, J., Moretti, M., & Franzoso, G. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.08.001 · Cited by 461
Hypoxia: Overview on Hypoxia-Mediated Mechanisms with a Focus on the Role of HIF Genes
Tirpe, A., Gulei, D., Ciortea, S. M., Crivii, C. B., & Berindan‐Neagoe, I. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20246140 · Cited by 451
“HIF-1α and HIF-2α have different expression profiles and different targets.”
BackgroundInfluentialOxygen availability and metabolic adaptations
Nakazawa, M. S., Keith, B., & Simon, M. C. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.84 · Cited by 446
Self-citationPersonalized Management of Pheochromocytoma and Paraganglioma
Nölting, S., Bechmann, N., Taïeb, D., Beuschlein, F., Faßnacht, M., Kroiß, M., Eisenhofer, G., Grossman, A. B., & Pacák, K. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab019 · Cited by 441
“Through HIF-α stabilization, cluster 1 mutations promote angiogenesis (eg, vascular endothelial growth factor (VEGF)/PDGF transcription), tumor extravasation, migration, invasion, metastasis, and other cellular processes (49-51).”
BackgroundMetabolic control of epigenetics in cancer
Kinnaird, A. S., Zhao, S., Wellen, K. E., & Michelakis, E. D. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.82 · Cited by 429
Hypoxia, Hypoxia-inducible Transcription Factors, and Renal Cancer
Schödel, J., Grampp, S., Maher, E. R., Moch, H., Ratcliffe, P. J., Russo, P., & Mole, D. R. (2015) · European Urology · doi:10.1016/j.eururo.2015.08.007 · Cited by 420
The role of hypoxia-inducible factors in metabolic diseases
Gonzalez, F. J., Xie, C., & Jiang, C. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0096-z · Cited by 416
Somatic HIF2A Gain-of-Function Mutations in Paraganglioma with Polycythemia
Zhuang, Z., Yang, C., Lorenzo, F., Merino, M., Fojo, T., Kebebew, E., Popovic, V., Stratakis, C. A., Prchal, J. T., & Pacak, K. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1205119 · Cited by 397
Qiu, B., Ackerman, D., Sanchez, D. J., Li, B., Ochocki, J. D., Grazioli, A., Bobrovnikova-Marjon, E., Diehl, J. A., Keith, B., & Simon, M. C. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1507 · Cited by 394
Self-citationThe VHL/HIF axis in clear cell renal carcinoma
Shen, C., & Kaelin, W. G. (2012) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2012.06.001 · Cited by 404
The IRP/IRE system in vivo: insights from mouse models
Wilkinson, N., & Pantopoulos, K. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00176 · Cited by 366
“THE IRE/IRP SYSTEM IN CANCER Considering that HIF2α may function either as a tumor promoter or suppressor (Keith et al., 2012), the regulation of HIF2α mRNA translation by IRP1 provides a link between the IRE/IRP system and cancer biology.”
BackgroundRedox control of inflammation in macrophages
Brüne, B., Dehne, N., Grossmann, N., Jung, M., Namgaladze, D., Schmid, T., von Knethen, A., & Weigert, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4785 · Cited by 377
Singhal, R., & Shah, Y. M. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.011188 · Cited by 401
González-Ávila, G., Sommer, B., Mendoza-Posada, D. A., Ramos, C., García-Hernández, A. A., & Falfán‐Valencia, R. (2019) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2019.02.010 · Cited by 393
Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells
Fendt, S.-M., Bell, E. L., Keibler, M. A., Olenchock, B. A., Mayers, J. R., Wasylenko, T. M., Vokes, N. I., Guarente, L., Heiden, M. G. V., & Stephanopoulos, G. (2013) · Nature Communications · doi:10.1038/ncomms3236 · Cited by 364
Structural integration in hypoxia-inducible factors
Wu, D., Potluri, N., Lu, J., Kim, Y., & Rastinejad, F. (2015) · Nature · doi:10.1038/nature14883 · Cited by 346
Targeting hypoxia signalling for the treatment of ischaemic and inflammatory diseases
Eltzschig, H. K., Bratton, D. L., & Colgan, S. P. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4422 · Cited by 364
Cotte, A. K., Aires, V., Fredon, M., Limagne, E., Dérangère, V., Thibaudin, M., Humblin, É., Scagliarini, A., de Barros, J.-P. P., Hillon, P., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02732-5 · Cited by 365
Vascular Permeability and Drug Delivery in Cancers
Azzi, S., Hebda, J. K., & Gavard, J. (2013) · Frontiers in Oncology · doi:10.3389/fonc.2013.00211 · Cited by 379
Human high-altitude adaptation: forward genetics meets the HIF pathwayPreprint
Bigham, A. W., & Lee, F. S. (2014) · Genes & Development · doi:10.1101/gad.250167.114 · Cited by 364
“For example, HIF-1a promotes cell cycle arrest, whereas HIF-2a promotes progression through the cell cycle, likely in a cell context-dependent manner (Keith et al. 2012).”
BackgroundA Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma
Wallace, E. M., Rizzi, J. P., Han, G., Wehn, P. M., Cao, Z., Du, X., Cheng, T., Czerwinski, R. M., Dixon, D. D., Goggin, B. S., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0473 · Cited by 336
Hypoxia‐inducible factors in regulation of immune responses in tumour microenvironment
Kumar, V., & Gabrilovich, D. I. (2014) · Immunology · doi:10.1111/imm.12380 · Cited by 329
Hypoxia-inducible factors and the regulation of lipid metabolism
Mylonis, I., Simos, G., & Paraskeva, E. (2019) · Cells · doi:10.3390/cells8030214 · Cited by 316
The Role of Hypoxia in Glioblastoma Invasion
Monteiro, A. R., Hill, R., Pilkington, G. J., & Madureira, P. A. (2017) · Cells · doi:10.3390/cells6040045 · Cited by 333
“HIFs are heterodimeric complexes constituted by O2-regulated α subunits (HIF-1α, EPAS1/HIF-2α, or HIF-3α) and a constitutively expressed β subunit, HIF-1β, also known as an aryl hydrocarbon receptor nuclear translocator (ARNT) [34,35].”
BackgroundGameiro, P. A., Yang, J., Metelo, A. M., Pérez-Carro, R., Baker, R., Wang, Z., Arreola, A., Rathmell, W. K., Olumi, A., López-Larrubia, P., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.02.002 · Cited by 325
Allosteric inhibition of hypoxia inducible factor-2 with small molecules
Scheuermann, T. H., Li, Q., Ma, H.-W., Key, J., Zhang, L., Chen, R., Garcia, J. A., Naidoo, J., Longgood, J., Frantz, D. E., et al. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1185 · Cited by 315
Anaemia in kidney disease: harnessing hypoxia responses for therapy
Koury, M. J., & Haase, V. H. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.82 · Cited by 313
CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape
Rodríguez-García, A., Palazón, A., Noguera-Ortega, E., Powell, D. J., & Guedan, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01109 · Cited by 326
“This family of transcription factors is mainly comprised of two isoforms: HIF-1α and HIF-2α (107), with HIF-1α being the main isoform expressed by activated T cells (108).”
BackgroundMechanisms of hypoxia signalling: new implications for nephrology
Schödel, J., & Ratcliffe, P. J. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0182-z · Cited by 309
Oxygen sensing and hypoxia signalling pathways in animals: The implications of physiology for cancer
Ratcliffe, P. J. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.251470 · Cited by 294
“Interestingly, in support of an antitumourigenic action of HIF-1α in this context, human VHL-defective CCRC is associated with a high prevalence of copy number reduction for a region of chromosome 14q containing HIF-1α, amongst other genes (Shen et al. 2011).”
BackgroundInfluentialHypoxia-driven pathways in bone development, regeneration and disease
Maes, C., Carmeliet, G., & Schipani, E. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2012.36 · Cited by 306
Hypoxia-Induced Epithelial-Mesenchymal Transition in Cancers: HIF-1α and Beyond
Tam, S. Y., Wu, V., & Law, H. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00486 · Cited by 319
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
SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer
Eifler, K., & Vertegaal, A. C. O. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.09.006 · Cited by 298
The EGLN-HIF O 2 -Sensing System: Multiple Inputs and Feedbacks
Ivan, M., & Kaelin, W. G. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.06.002 · Cited by 273
PHENOTYPIC PLASTICITY AND EPIGENETIC MARKING: AN ASSESSMENT OF EVIDENCE FOR GENETIC ACCOMMODATION
Schlichting, C. D., & Wund, M. A. (2014) · Evolution · doi:10.1111/evo.12348 · Cited by 295
“These responses to hypoxia are mediated by the hypoxia-inducible factor (HIF) signaling cascade, which affects expression of genes involved in erythrocyte production, glycolysis, pH homeostasis, lipid metabolism, and the formation of new blood vessels (Chen et al. 2012a; Keith et al. 2012).”
BackgroundTargeting the Tumor Microenvironment: From Understanding Pathways to Effective Clinical Trials
Hua, F., & DeClerck, Y. A. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-0661 · Cited by 286
Bersten, D. C., Sullivan, A. E., Peet, D. J., & Whitelaw, M. L. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3621 · Cited by 267
Tang, Y.-A., Chen, Y.-F., Bao, Y., Mahara, S., Yatim, S. M. J. M., Oguz, G., Lee, P. L., Feng, M., Cai, Y., Tan, E. Y., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1801348115 · Cited by 277
“Hypoxia, a critical feature in the tumor microenvironment, has been shown to promote cancer stemness through the hypoxiainducible factors (HIFs) (15, 16).”
BackgroundLoss of the Tumor Suppressor LKB1 Promotes Metabolic Reprogramming of Cancer Cells via HIF-1α
Faubert, B., Vincent, E. E., Griss, T., Samborska, B., Izreig, S., Svensson, R. U., Mamer, O. A., Avizonis, D., Shackelford, D. B., Shaw, R. J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1312570111 · Cited by 278
Oxidative stress and metal carcinogenesis
Lee, J., Son, Y., Pratheeshkumar, P., & Shi, X. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.06.002 · Cited by 279
Collagen prolyl 4-hydroxylase 1 is essential for HIF-1α stabilization and TNBC chemoresistance
Xiong, G., Stewart, R. L., Chen, J., Gao, T., Scott, T. L., Samayoa, L. M., O’Connor, K. L., Lane, A. N., & Xu, R. (2018) · Nature Communications · doi:10.1038/s41467-018-06893-9 · Cited by 283
Hypoxia-inducible factor 3 biology: complexities and emerging themes
Duan, C. (2016) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00315.2015 · Cited by 269
Pathophysiological implications of hypoxia in human diseases
Chen, P.-S., Chiu, W.-T., Hsu, P.-L., Lin, S.-C., Peng, I.-C., Wang, C.-Y., & Tsai, S.-J. (2020) · Journal of Biomedical Science · doi:10.1186/s12929-020-00658-7 · Cited by 318
“In vitro experiments show that HIF-1α and HIF-2α inhibit insulin signaling in both human and murine white adipocytes [120].”
BackgroundInfluentialWu, Q., Zhou, W., Yin, S., Zhou, Y., Chen, T., Qian, J., Su, R., Hong, L., Lu, H., Zhang, F., et al. (2019) · Hepatology · doi:10.1002/hep.30593 · Cited by 272
“It is clear that the rapid growth of solid tumors contributes to the hypoxic environment and elevates the expression of HIFs.(1,24) In accordance, the HIF-1α level gradually increased during tumor growth in an orthotopic liver tumor model (Fig.”
BackgroundDirect regulation of GAS6/AXL signaling by HIF promotes renal metastasis through SRC and MET
Rankin, E. B., Fuh, K. C., Castellini, L., Viswanathan, K., Finger, E. C., Diep, A. N., LaGory, E. L., Kariolis, M. S., Chan, A., Lindgren, D., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1404848111 · Cited by 269
The Mitochondrial Chaperone TRAP1 Promotes Neoplastic Growth by Inhibiting Succinate Dehydrogenase
Sciacovelli, M., Guzzo, G., Morello, V., Frezza, C., Zheng, L., Nannini, N., Calabrese, F., Laudiero, G., Esposito, F., Landriscina, M., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.019 · Cited by 272
Microenvironment and tumor cell plasticity: An easy way out
Taddei, M. L., Giannoni, E., Comito, G., & Chiarugi, P. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.01.042 · Cited by 272
Hypoxia-responsive nanoparticle based drug delivery systems in cancer therapy: An up-to-date review
KUMARI, R. R., Sunil, D., & Ningthoujam, R. S. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.12.041 · Cited by 273
Caveolin-1 in the regulation of cell metabolism: a cancer perspective
Nwosu, Z. C., Ebert, M., Dooley, S., & Meyer, C. (2016) · Molecular Cancer · doi:10.1186/s12943-016-0558-7 · Cited by 257
“regulators of genes encoding glycolytic enzymes, glucose transporters, and also mediators of angiogenesis and tumour metastasis [53].”
BackgroundThe multicellular tumor spheroid model for high-throughput cancer drug discovery
LaBarbera, D. V., Reid, B. G., & Yoo, B. H. (2012) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2012.708334 · Cited by 264
HIF-1 in cancer therapy: two decade long story of a transcription factor
Soni, S., & Padwad, Y. S. (2017) · Acta Oncologica · doi:10.1080/0284186x.2017.1301680 · Cited by 251
Targeting iron metabolism in cancer therapy
Morales, M., & Xue, X. (2021) · Theranostics · doi:10.7150/thno.59092 · Cited by 262
“On the other hand, HIF-2α appears to be the more dominantly active isoform during a prolonged hypoxic response [33-35].”
BackgroundMelanocytic nevi and melanoma: unraveling a complex relationship
Damsky, W., & Bosenberg, M. (2017) · Oncogene · doi:10.1038/onc.2017.189 · Cited by 263
Oxidative Stress and the Homeodynamics of Iron Metabolism
Bresgen, N., & Eckl, P. (2015) · Biomolecules · doi:10.3390/biom5020808 · Cited by 247
Yang, Z., Su, W., Wei, X., Qu, S., Zhao, D., Zhou, J., Wang, Y., Guan, Q., Qin, C., Xiang, J. Y., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112945 · Cited by 261
Qiu, G., Jin, M., Dai, J., Sun, W., Feng, J., & Jin, W. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.05.002 · Cited by 250
Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche
Clever, D. C., Roychoudhuri, R., Constantinides, M. G., Askenase, M. H., Sukumar, M., Klebanoff, C. A., Eil, R. L., Hickman, H. D., Yu, Z., Pan, J. H., et al. (2016) · Cell · doi:10.1016/j.cell.2016.07.032 · Cited by 246
“HIF has been shown to increase proliferation in some cancer types (Keith et al., 2012).”
BackgroundSUMO-targeted ubiquitin ligases
Sriramachandran, A. M., & Dohmen, R. J. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.08.022 · Cited by 241
Pérgola, P. E., Spinowitz, B., Hartman, C., Maroni, B. J., & Haase, V. H. (2016) · Kidney International · doi:10.1016/j.kint.2016.07.019 · Cited by 242
Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine
Briggs, K. J., Koivunen, P., Cao, S., Backus, K. M., Olenchock, B. A., Patel, H., Zhang, Q. H., Signoretti, S., Gerfen, G. J., Richardson, A. L., et al. (2016) · Cell · doi:10.1016/j.cell.2016.05.042 · Cited by 228
McNamee, E. N., Korns Johnson, D., Homann, D., & Clambey, E. T. (2013) · Immunologic Research · doi:10.1007/s12026-012-8349-8 · Cited by 234
Current and future immunotherapeutic approaches in pancreatic cancer treatment
Farhangnia, P., Khorramdelazad, H., Nickho, H., & Delbandi, A. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01561-6 · Cited by 265
Takahashi, K., Yan, I. K., Haga, H., & Patel, T. C. (2014) · Journal of Cell Science · doi:10.1242/jcs.141069 · Cited by 231
“Levels of HIF-1a are generally increased in aggressive tumors (Keith et al., 2012) and could be useful as a molecular predictor of poor prognosis and treatment response in HCC (Xiang et al., 2011; Nath and Szabo, 2012; Zheng et al., 2013).”
Background
Metadata
- Authors
- Keith, B., Johnson, R. S., & Simon, M. C.
- Affiliations
- Abramson Cancer Center (US)
- University of California San Diego (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Simon, M. Celeste
- Venue
- Nature Reviews Cancer
- Published
- 2011-12-15
- Volume
- 12
- Issue
- 1
- Pages
- 9-22
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- PMC
- PMC3401912
- OpenAlex
- W1998664010
- Cited by
- 1,693
- References
- 197
- Citations by year
- 2026: 82 · 2025: 82 · 2024: 112 · 2023: 116 · 2022: 126 · 2021: 135 · 2020: 118 · 2019: 124 · 2018: 123 · 2017: 117 · 2016: 112 · 2015: 112 · 2014: 141 · 2013: 122 · 2012: 70
- FWCI
- 7.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Wellcome Trust (092738/Z/10/Z)
- National Heart, Lung, and Blood Institute (R01HL066310)
- National Cancer Institute (R01CA158301)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- HIF-1α, HIF-2α, hypoxia-inducible factor, tumor hypoxia, tumor progression, HIF target genes, c-Myc, p53, HIF inhibitors, cancer therapeutics, oxygen sensing
- MeSH terms
- Mechanistic Target of Rapamycin Complex 1, Endothelial PAS Domain-Containing Protein 1, Acetylation, Animals, Gene Expression Regulation, Humans, Neoplasms, Protein Processing, Post-Translational, Proteins, Cell Hypoxia, Genes, p53, Genes, myc, Disease Progression, Multiprotein Complexes, Cell Proliferation, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, TOR Serine-Threonine Kinases
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
