Suppression of the Hypoxia-Inducible Factor-1 Response in Cervical Carcinoma Xenografts by Proteasome Inhibitors
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Abstract
Experimental data suggest therapeutic advantage from selective disruption of the hypoxia response. We recently found that the proteasome inhibitor bortezomib decreases tumor carbonic anhydrase IX (CAIX) expression in colon cancer patients and herein report a companion laboratory study to test if this effect was the result of hypoxia-inducible factor (HIF) inhibition. Human cervical (SiHa and Me180) and colon (RKO) carcinoma cell lines were treated with bortezomib or the structurally unrelated proteasome inhibitor MG132 in normoxic and hypoxic conditions in vitro. Two different in vivo experiments investigated bortezomib effects after single dose (2 mg/kg, 24 h) or longer exposure in severe combined immunodeficient mice bearing SiHa xenografts. Treatment with either drug produced accumulation of HIF-1alpha in vitro but strongly inhibited the production of CAIX and vascular endothelial growth factor (VEGF) under hypoxia. This correlated with more than 10-fold reduction in HIF-1 transcriptional activity under hypoxic conditions. A similar effect of bortezomib was seen in vivo, using the nitroimidazole probe EF5 to define regions of tumor hypoxia and a triple immunofluorescence technique to measure the spatial distributions of HIF-1alpha and CAIX. Plasma VEGF levels decreased by approximately 90% during treatment with bortezomib, indicating that this agent can potently inhibit the hypoxia response in tumors.
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Bortezomib is associated with suppression of HIF-1 signaling despite expectation that proteasome inhibition would stabilize HIF-α subunits.
“bortezomib, a clinically approved proteasome inhibitor used in multiple myeloma, has been repeatedly associated with suppression of HIF-1 signaling, despite the expectation that proteasome inhibition would stabilize HIF-α subunits [[336], [337], [338]].”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [337]
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Cites
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717 · see citing works
Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333 · see citing works
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 · see citing works
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068 · see citing works
Salceda, S., & Caro, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22642 · Cited by 1,674 · see citing works
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× · see citing works
“FIH-1 (the inhibiting factor of HIF-1) is an asparaginyl hydroxylase that binds to the HIF-1a–VHL complex> and controls HIF-1 transactivation by obstructing the recruitment of CBP/p300 coactivators (16, 36, 46).”
Mahon, P. C., Hirota, K., & Semenza, G. L. (2001) · Genes & Development · doi:10.1101/gad.924501 · Cited by 1,385 · see citing works
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 · see citing works
The proteasome: a suitable antineoplastic target
Adams, J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1361 · Cited by 1,200 · see citing works
Appelhoff, R. J., Tian, Y.-M., Raval, R. R., Turley, H., Harris, A. L., Pugh, C. W., Ratcliffe, P. J., & Gleadle, J. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406026200 · Cited by 1,108 · see citing works
Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha.
Ravi, R. K., Mookerjee, B., Bhujwalla, Z. M., Sutter, T. R., Artemov, D., Zeng, Q., Dillehay, L. E., Madan, A., Semenza, G. L., & Bedi, A. (2000) · PubMed Central · Cited by 1,099 · see citing works
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 · see citing works
Signal transduction to hypoxia-inducible factor 1
Semenza, G. L. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)01168-1 · Cited by 860 · see citing works
Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor
Hirsilä, M., Koivunen, P., Günzler, V., Kivirikko, K. I., & Myllyharju, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304982200 · Cited by 794 · see citing works
Structure of an HIF-1α-pVHL Complex: Hydroxyproline Recognition in Signaling
Min, J.-H., Yang, H., Ivan, M., Gertler, F., Kaelin, W. G., & Pavletich, N. P. (2002) · Science · doi:10.1126/science.1073440 · Cited by 765 · see citing works
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 · see citing works
Structural basis for the recognition of hydroxyproline in HIF-1α by pVHL
Hon, W.-C., Wilson, M. I., Harlos, K., Claridge, T. D. W., Schofield, C. J., Pugh, C. W., Maxwell, P. H., Ratcliffe, P. J., Stuart, D. I., & Jones, E. Y. (2002) · Nature · doi:10.1038/nature00767 · Cited by 751 · see citing works
Regulation and Destabilization of HIF-1α by ARD1-Mediated Acetylation
Jeong, J.-W., Bae, M.-K., Ahn, M.-Y., Kim, S.-H., Sohn, T.-K., Bae, M.-H., Yoo, M.-A., Song, E. J., Lee, K.-J., & Kim, K.-W. (2002) · Cell · doi:10.1016/s0092-8674(02)01085-1 · Cited by 716 · see citing works
Ema, M., Hirota, K., Mimura, J., Abe, H., Yodoi, J., Sogawa, K., Poellinger, L., & Fujii‐Kuriyama, Y. (1999) · The EMBO Journal · doi:10.1093/emboj/18.7.1905 · Cited by 588 · see citing works
Sunwoo, J. B., Chen, Z., Dong, G., Yeh, N. T., Bancroft, C. C., Sausville, E. A., Adams, J., Elliott, P. J., & Waes, C. V. (2001) · PubMed · Cited by 473 · see citing works
Intracellular localisation of human HIF-1α hydroxylases:implications for oxygen sensing
Metzen, E., Berchner-Pfannschmidt, U., Stengel, P., Marxsen, J. H., Stolze, I., Klinger, M., Huang, W. Q., Wotzlaw, C., Hellwig-Bürgel, T., Jelkmann, W., et al. (2003) · Journal of Cell Science · doi:10.1242/jcs.00318 · Cited by 432 · see citing works
Nakayama, K., Frew, I. J., Hagensen, M. K., Skals, M., Habelhah, H., Bhoumik, A., Kadoya, T., Erdjument‐Bromage, H., Tempst, P., Frappell, P. B., et al. (2004) · Cell · doi:10.1016/j.cell.2004.06.001 · Cited by 405 · see citing works
MARXSEN, J. H., STENGEL, P., DOEGE, K., HEIKKINEN, P., JOKILEHTO, T., WAGNER, T., JELKMANN, W., JAAKKOLA, P., & METZEN, E. (2004) · Biochemical Journal · doi:10.1042/bj20040620 · Cited by 386 · see citing works
HIF hydroxylation and the mammalian oxygen-sensing pathway
Safran, M., & Kaelin, W. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18181 · Cited by 363 · see citing works
Hypoxia Up-regulates Prolyl Hydroxylase Activity
D’Angelo, G., Duplan, E., Boyer, N., Vigne, P., & Frelin, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302244200 · Cited by 285 · see citing works
p53 Inhibits Hypoxia-inducible Factor-stimulated Transcription
Blagosklonny, M. V., An, W. G., Romanova, L. Y., Trepel, J. B., Fojo, T., & Neckers, L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.20.11995 · Cited by 284 · see citing works
Negative and positive regulation of HIF-1: A complex network
Bárdos, J. I., & Ashcroft, M. A. (2005) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2005.05.001 · Cited by 282 · see citing works
Role of Prolyl Hydroxylation in Oncogenically Stabilized Hypoxia-inducible Factor-1α
Chan, D. A., Sutphin, P. D., Denko, N. C., & Giaccia, A. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206922200 · Cited by 264 · see citing works
Effect of desferrioxamine and metals on the hydroxylases in the oxygen sensing pathway
Hirsilä, M., Koivunen, P., Xu, L., Seeley, T. W., Kivirikko, K. I., & Myllyharju, J. (2005) · The FASEB Journal · doi:10.1096/fj.04-3399fje · Cited by 220 · see citing works
Baek, J. H., Mahon, P. C., Oh, J. C., Kelly, B., Krishnamachary, B., Pearson, M., Chan, D. A., Giaccia, A. J., & Semenza, G. L. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.01.011 · Cited by 218 · see citing works
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 213 · see citing works
Regulation of HIF prolyl hydroxylases by hypoxia‐inducible factors
Aprelikova, O. N., Chandramouli, G. V. R., Wood, M. J. A., Vasselli, J. R., Riss, J., Maranchie, J. K., Linehan, W. M., & Barrett, J. C. (2004) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20067 · Cited by 212 · see citing works
Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells
Meng, A. X., Jalali, F., Cuddihy, A. R., Chan, N. H. L., Bindra, R. S., Glazer, P. M., & Bristow, R. G. (2005) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2005.06.025 · Cited by 195 · see citing works
The ubiquitin‐proteasome pathway
Roos‐Mattjus, P., & Sistonen, L. (2004) · Annals of Medicine · doi:10.1080/07853890310016324 · Cited by 185 · see citing works
Nawrocki, S. T., Bruns, C. J., Harbison, M. T., Bold, R. J., Sweeney‐Gotsch, B., Abbruzzese, J. L., Elliott, P. J., Adams, J., & McConkey, D. J. (2002) · PubMed · Cited by 170 · see citing works
Williams, S. A., Pettaway, C. A., Song, R., Papandreou, C. N., Logothetis, C. J., & McConkey, D. J. (2003) · PubMed · Cited by 164 · see citing works
Novel Mechanism of Action for Hydralazine
Knowles, H. J., Tian, Y., Mole, D. R., & Harris, A. L. (2004) · Circulation Research · doi:10.1161/01.res.0000134924.89412.70 · Cited by 143 · see citing works
p300 relieves p53-evoked transcriptional repression of hypoxia-inducible factor-1 (HIF-1)
Schmid, T., Zhou, J., Köhl, R., & Brüne, B. (2004) · Biochemical Journal · doi:10.1042/bj20031299 · Cited by 138 · see citing works
Kaluz, S., Kaluzová, M., & Stanbridge, E. J. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00552-06 · Cited by 108 · see citing works
Determination and comparison of specific activity of the HIF‐prolyl hydroxylases
Tuckerman, J. R., Zhao, Y., Hewitson, K. S., Tian, Y., Pugh, C. W., Ratcliffe, P. J., & Mole, D. R. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.09.005 · Cited by 105 · see citing works
MacKay, H. J., Hedley, D. W., Major, P. P., Townsley, C. A., MacKenzie, M. J., Vincent, M. D., Degendorfer, P., Tsao, M., Nicklee, T., Birle, D. C., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0081 · Cited by 103 · see citing works
Self-citationKnowles, H. J., Mole, D. R., Ratcliffe, P. J., & Harris, A. L. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2351 · Cited by 94 · see citing works
Hypoxia-inducible factor-1alpha is an intrinsic marker for hypoxia in cervical cancer xenografts.
Vukovic, V. M., Haugland, H. K., Nicklee, T., Morrison, A. J., & Hedley, D. W. (2001) · PubMed · Cited by 91 · see citing works
Self-citationMdm2 and HIF‐1α interaction in tumor cells during hypoxia
Nieminen, A., Qanungo, S., Schneider, E., Jiang, B., & Agani, F. H. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20406 · Cited by 88 · see citing works
Hougardy, B. M. T., Maduro, J. H., van der Zee, A. G. J., de Groot, D. J. A., van den Heuvel, F. A. J., de Vries, E. G. E., & de Jong, S. (2005) · International Journal of Cancer · doi:10.1002/ijc.21580 · Cited by 60 · see citing works
Activation of HIF-prolyl Hydroxylases by R59949, an Inhibitor of the Diacylglycerol Kinase
Temes, E., Martı́n-Puig, S., Acosta‐Iborra, B., Castellanos, M. C., Feijoo‐Cuaresma, M., Olmos, G., Aragonés, J., & Landázuri, M. O. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414694200 · Cited by 59 · see citing works
Accumulation of hypoxia-inducible factor-1α is limited by transcription-dependent depletion
Demidenko, Z. N., Rapisarda, A., Garayoa, M., Giannakakou, P., Melillo, G., & Blagosklonny, M. V. (2005) · Oncogene · doi:10.1038/sj.onc.1208636 · Cited by 51 · see citing works
Activation of hypoxia-induced transcription in normoxia
Hägg, M., & Wennström, S. (2005) · Experimental Cell Research · doi:10.1016/j.yexcr.2005.01.017 · Cited by 47 · see citing works
When hypoxia signalling meets the ubiquitin-proteasomal pathway, new targets for cancer therapy
Brahimi‐Horn, C., & Pouysségur, J. (2004) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2004.09.003 · Cited by 36 · see citing works
Latonen, L., Kurki, S., Pitkänen, K., & Laiho, M. (2003) · Cellular Signalling · doi:10.1016/s0898-6568(02)00044-x · Cited by 35 · see citing works
The role of proteasome inhibitors in solid tumors
Park, D. S., & Lenz, H. (2004) · Annals of Medicine · doi:10.1080/07853890410029031 · Cited by 31 · see citing works
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Hypoxia signalling through mTOR and the unfolded protein response in cancer
Wouters, B. G., & Koritzinsky, M. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2501 · Cited by 894 · see citing works
Hypoxia signaling in human health and diseases: implications and prospects for therapeutics
Luo, Z., Tian, M., Yang, G., Tan, Q., Chen, Y., Li, G., Zhang, Q., Li, Y., Wan, P., & Wu, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01080-1 · Cited by 499 · see citing works
Mechanisms of proteasome inhibitor action and resistance in cancer
McConkey, D. J., & Zhu, K. (2008) · Drug Resistance Updates · doi:10.1016/j.drup.2008.08.002 · Cited by 309 · see citing works
Milani, M., Rzymski, T., Mellor, H. R., Pike, L., Bottini, A., Generali, D., & Harris, A. L. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-2839 · Cited by 304 · see citing works
Kaluz, Š., Kaluzová, M., Liao, S., Lerman, M. I., & Stanbridge, E. J. (2009) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2009.01.001 · Cited by 251 · see citing works
Potts, B. C. M., Albitar, M. X., Anderson, K. C., Baritaki, S., Berkers, C. R., Bonavida, B., Chandra, J., Chauhan, D., Cusack, J. C., Fenical, W., et al. (2011) · Current Cancer Drug Targets · doi:10.2174/156800911794519716 · Cited by 247 · see citing works
Therapy of Human Papillomavirus-Related Disease
Stern, P. L., van der Burg, S. H., HAMPSON, I. N., Broker, T. R., Fiander, A., Lacey, C. J., Kitchener, H. C., & Einstein, M. H. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.05.091 · Cited by 178 · see citing works
Kaluz, Š., Kaluzová, M., & Stanbridge, E. J. (2008) · Clinica Chimica Acta · doi:10.1016/j.cca.2008.05.002 · Cited by 171 · see citing works
Shin, D. H., Chun, Y., Lee, D. S., Huang, E. L., & Park, J. (2008) · Blood · doi:10.1182/blood-2007-11-120576 · Cited by 163 · see citing works
Unfolded protein response (UPR) integrated signaling networks determine cell fate during hypoxia
Bartoszewska, S., & Collawn, J. F. (2020) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-020-00212-1 · Cited by 150 · see citing works
Befani, C. D., Vlachostergios, P. J., Hatzidaki, E., Patrikidou, A., Bonanou, S., Simos, G., Papandreou, C. N., & Liakos, P. (2012) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0805-8 · Cited by 135 · see citing works
Lim, J.-H., Chun, Y., & Park, J. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6234 · Cited by 112 · see citing works
Grantab, R., & Tannock, I. F. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-214 · Cited by 90 · see citing works
FAS-Associated Factor 1 (FAF1): Diverse functions and implications for oncogenesis
Menges, C. W., Altomare, D. A., & Testa, J. R. (2009) · Cell Cycle · doi:10.4161/cc.8.16.9280 · Cited by 90 · see citing works
Proteasome inhibition: A new therapeutic strategy to cancer treatment
Wu, W. K. K., Cho, C. H., Lee, C. W., Wu, K., Fan, D., Yu, J. Q., & Sung, J. J. �. (2010) · Cancer Letters · doi:10.1016/j.canlet.2009.12.002 · Cited by 86 · see citing works
Zhou, J., Zhang, S., Xue, J., Avery, J. E., Wu, J., Lind, S. E., & Ding, W. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.367367 · Cited by 77 · see citing works
Immunomodulatory effects of anti-angiogenic drugs
Heine, A., Held, S., Bringmann, A., Holderried, T. A. W., & Brossart, P. (2011) · Leukemia · doi:10.1038/leu.2011.24 · Cited by 76 · see citing works
An Overview of the Recent Development of Anticancer Agents Targeting the HIF-1 Transcription Factor
Shirai, Y., Chow, C. C. T., Kambe, G., Suwa, T., Kobayashi, M., Takahashi, I., Harada, H., & Nam, J. (2021) · Cancers · doi:10.3390/cancers13112813 · Cited by 74 · see citing works
Yoshii, Y., Furukawa, T., Waki, A., Okuyama, H., Inoue, M., Itoh, M., Zhang, M.-R., Wakizaka, H., Sogawa, C., Kiyono, Y., et al. (2015) · Biomaterials · doi:10.1016/j.biomaterials.2015.02.008 · Cited by 66 · see citing works
Control of HIF-1α Expression by eIF2α Phosphorylation–Mediated Translational Repression
Zhu, K., Chan, W., Heymach, J., Wilkinson, M., & McConkey, D. J. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4103 · Cited by 55 · see citing works
Mitochondrial dysfunction, UPRmt signaling, and targeted therapy in metastasis tumor
Keerthiga, R., Pei, D., & Fu, A. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00696-0 · Cited by 53 · see citing works
Hu, Y., Kirito, K., Yoshida, K., Mitsumori, T., Nakajima, K., Nozaki, Y., Hamanaka, S., Nagashima, T., Kunitama, M., Sakoe, K., et al. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0150 · Cited by 52 · see citing works
de Freitas, N. L., Deberaldini, M. G., Gomes, D., Pavan, A. R., Sousa, Â., dos Santos, J. L., & Soares, C. P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.592868 · Cited by 45 · see citing works
Proteasome inhibition with bortezomib suppresses growth and induces apoptosis in osteosarcoma
Shapovalov, Y., Benavidez, D., Zuch, D. T., & Eliseev, R. A. (2009) · International Journal of Cancer · doi:10.1002/ijc.25024 · Cited by 44 · see citing works
Zhao, S., Su, X.-L., Pan, R.-J., Lu, L., Zheng, G., & Zou, S. (2022) · BMC Genomics · doi:10.1186/s12864-022-08399-7 · Cited by 41 · see citing works
Targeting NF-κB and HIF-1 Pathways for the Treatment of Cancer: Part II
Wilczynski, J., Duechler, M., & Czyz, M. (2011) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-011-0132-3 · Cited by 41 · see citing works
Kang, M. J., Jung, S. M., Kim, M. J., Bae, J. H., Kim, H. B., Kim, J. Y., Park, S. J., Song, H. S., Kim, D. W., Kang, C., et al. (2008) · FEBS Journal · doi:10.1111/j.1742-4658.2008.06725.x · Cited by 36 · see citing works
CITED2 mediates the paradoxical responses of HIF-1α to proteasome inhibition
Shin, D. H., Li, S., Chun, Y.-S., Huang, E. L., Kim, M.-S., & Park, J.-W. (2007) · Oncogene · doi:10.1038/sj.onc.1210826 · Cited by 35 · see citing works
Yoon, H., Lim, J.-H., Cho, C., Huang, E. L., & Park, J. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.08.018 · Cited by 35 · see citing works
Bortezomib attenuates HIF-1- but not HIF-2-mediated transcriptional activation
ABD-AZIZ, N., STANBRIDGE, E. J., & SHAFEE, N. (2015) · Oncology Letters · doi:10.3892/ol.2015.3545 · Cited by 31 · see citing works
Hypoxia-inducible factors: Crosstalk between their protein stability and protein degradation
Wei, W., & Yu, X. D. (2007) · Cancer Letters · doi:10.1016/j.canlet.2007.08.009 · Cited by 31 · see citing works
Pham, N., Magalhaes, J., Do, T., Schwock, J., Dhani, N. C., Cao, P., Hill, R. P., & Hedley, D. W. (2008) · International Journal of Cancer · doi:10.1002/ijc.23912 · Cited by 29 · see citing works
Self-citationLiang, J., Nishi, H., Bian, M., Higuma, C., Sasaki, T., Ito, H., & Isaka, K. (2012) · Oncology Reports · doi:10.3892/or.2012.1949 · Cited by 29 · see citing works
Kaluz, Š., Kaluzová, M., & Stanbridge, E. J. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21644 · Cited by 27 · see citing works
HIF gene expression in cancer therapy
Chan, D. A., Krieg, A. J., Turcotte, S., & Giaccia, A. J. (2007) · Methods in Enzymology · doi:10.1016/s0076-6879(07)35016-7 · Cited by 26 · see citing works
Targeting NF-κB and HIF-1 Pathways for the Treatment of Cancer: Part I
Wilczyński, J. R., Duechler, M., & Czyż, M. (2011) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-011-0131-4 · Cited by 26 · see citing works
Hsu, C.-W., Huang, R., Khuc, T., Shou, D., Bullock, J., Grooby, S., Griffin, S., Zou, C., Little, A. S., Astley, H. M., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.6995 · Cited by 26 · see citing works
Miyamoto, Y., Nakagawa, S., Wada‐Hiraike, O., Seiki, T., Tanikawa, M., Hiraike, H., Sone, K., Nagasaka, K., Oda, K., Kawana, K., et al. (2012) · Oncology Reports · doi:10.3892/or.2012.2072 · Cited by 25 · see citing works
Zuo (2010) · Molecular Medicine Reports · doi:10.3892/mmr_00000305 · Cited by 22 · see citing works
Wang, S., Hannafon, B. N., Wolf, R. F., Zhou, J., Avery, J. E., Wu, J., Lind, S. E., & Ding, W. (2014) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2013.12.011 · Cited by 21 · see citing works
Padrissa‐Altés, S., Zaoualí, M. A., Bartrons, R., & Roselló‐Catafau, J. (2012) · Clinical Science · doi:10.1042/cs20110093 · Cited by 21 · see citing works
Targeting the AKT pathway: Repositioning HIV protease inhibitors as radiosensitizers
Goda, J. S., Pachpor, T. A., Basu, T., Chopra, S., & Gota, V. (2016) · The Indian Journal of Medical Research · doi:10.4103/0971-5916.180201 · Cited by 17 · see citing works
Targeting the proteasome as a promising therapeutic strategy in thyroid cancer
Wunderlich, A. C., Arndt, T., Fischer, M., Roth, S., Ramaswamy, A., Greene, B., Brendel, C. A., Hinterseher, U., Bartsch, D. K., & Hoffmann, S. (2011) · Journal of Surgical Oncology · doi:10.1002/jso.22113 · Cited by 16 · see citing works
Understanding the relationship between cancer associated cachexia and hypoxia-inducible factor-1
Muthamil, S., Kim, H. Y., Jang, H., Lyu, J., Shin, U. C., Go, Y., Park, S., Lee, H. G., & Park, J. H. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114802 · Cited by 15 · see citing works
The expression of FAS-associated factor 1 and heat shock protein 70 in ovarian cancer
Kang, H.-J., Moon, H. S., & Chung, H. (2014) · Obstetrics & Gynecology Science · doi:10.5468/ogs.2014.57.4.281 · Cited by 15 · see citing works
The Bmi‐1/NF‐κB/VEGF story: another hint for proteasome involvement in glioma angiogenesis?
Vlachostergios, P. J., & Papandreou, C. N. (2013) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-013-0198-2 · Cited by 14 · see citing works
Koido, M., Haga, N., Furuno, A., Tsukahara, S., Sakurai, J., Tani, Y., Sato, S., & Tomida, A. (2017) · Oncotarget · doi:10.18632/oncotarget.14415 · Cited by 10 · see citing works
Progress towards the use of HIV proteases in cancer therapy
Bernhard, E. J., & Brunner, T. B. (2008) · Cancer Biology & Therapy · doi:10.4161/cbt.7.5.6087 · Cited by 9 · see citing works
Visualizing the antivascular effect of bortezomib on the hypoxic tumor microenvironment
Sun, X., Ackerstaff, E., He, F., Xing, L., Hsiao, H. T., Koutcher, J. A., Ling, C., & Li, G. C. (2015) · Oncotarget · doi:10.18632/oncotarget.5300 · Cited by 8 · see citing works
Roychowdhury, A., Pal, D., Basu, M., Samadder, S., Mondal, R. K., Roy, A. K., Roychoudhury, S., & Panda, C. K. (2023) · Cellular Signalling · doi:10.1016/j.cellsig.2023.110735 · Cited by 7 · see citing works
Thrombospondin-1 induction and VEGF reduction by proteasome inhibition
Bardag‐Gorce, F., Hoffman, C., Meepe, I., Ferrini, M. G., Hoft, R. H., Oliva, J., & Niihara, Y. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e13397 · Cited by 6 · see citing works
Bhavya, K., Agarwal, K., Negi, D., Niveria, K., Singh, Y., Verma, A. K., Dasgupta, S., Nirmalkar, N., & Pal, D. (2024) · ACS Applied Nano Materials · doi:10.1021/acsanm.4c05295 · Cited by 6 · see citing works
Lobo, M. R., Kukino, A., Tran, H. T. D., Schabel, M. C., SPRINGER, C. S. J., Gillespie, G. Y., Grafe, M. R., Woltjer, R. L., & Pike, M. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0144488 · Cited by 6 · see citing works
Herrera, F. G., Vidal, L., Oza, A. M., Milosevic, M., & Fyles, A. (2008) · Reviews on Recent Clinical Trials · doi:10.2174/157488708784223835 · Cited by 5 · see citing works
Comment on the role of FIH in the inhibitory effect of bortezomib on hypoxia-inducible factor-1
Kaluz, Š., Kaluzová, M., & Stanbridge, E. J. (2008) · Blood · doi:10.1182/blood-2008-02-140079 · Cited by 5 · see citing works
HIF inhibition: Current strategies and clinical challenges
Więch-Walów, A., Bartoszewska, S., Barton, A., Czechowicz, P., Dudzik, J., Wielockx, B., Collawn, J. F., & Bartoszewski, R. (2026) · Redox biology · doi:10.1016/j.redox.2026.104220 · Cited by 3 · see citing works
“…proposed mechanisms involving impaired recruitment of the transcriptional co-activator p300 - whether through factor inhibiting HIF (FIH)-dependent or FIH-independent pathways - may be secondary or even dispensable when nuclear accumulation of HIF-1 α is itself strongly inhibited [336,337,343].”
Potential drug targets against HPV and repurposing of existing drugs
Sahu, U., Khare, P. S., & Yadav, A. K. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91797-1.00007-7 · Cited by 1 · see citing works
Data from Control of HIF-1α Expression by eIF2α Phosphorylation–Mediated Translational Repression
Zhu, K., Chan, W., Heymach, J. V., Wilkinson, M., & McConkey, D. J. (2023) · doi:10.1158/0008-5472.c.6499688.v1
- Authors
- Birle, D. C., & Hedley, D. W.
- Affiliations
- 1Division of Applied Molecular Oncology, Ontario Cancer Institute and
- University of Toronto (CA)
- ORCID
- Hedley, David W.
- Venue
- Cancer Research
- Published
- 2007-02-15
- Volume
- 67
- Issue
- 4
- Pages
- 1735-1743
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2081753042
- Cited by
- 58
- References
- 51
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 1 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 2 · 2013: 1 · 2012: 6
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- HIF-1, HIF-1α, bortezomib, proteasome inhibitors, MG132, carbonic anhydrase IX, vascular endothelial growth factor, tumor hypoxia, cervical cancer, colon cancer, xenografts, HIF-1 transcriptional activity
- MeSH terms
- Bortezomib, Carbonic Anhydrase IX, Antigens, Neoplasm, Antineoplastic Agents, Boronic Acids, Carbonic Anhydrases, Carcinoma, Squamous Cell, Cell Nucleus, Uterine Cervical Neoplasms, Colonic Neoplasms, Enzyme Activation, Female, Humans, Leupeptins, Male, Prostatic Neoplasms, Protease Inhibitors, Protein Binding, Pyrazines, Cell Hypoxia, Xenograft Model Antitumor Assays, Vascular Endothelial Growth Factor A, Cell Line, Tumor, E1A-Associated p300 Protein, Hypoxia-Inducible Factor 1, alpha Subunit, Caspase 3
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