Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer
Open accessAbstract
Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of Polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway.
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
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?
Loss of PRC2-dependent histone H3 Lys-27 trimethylation activates HIF-mediated CXCR4 expression to promote invasion and metastasis.
“loss of polycomb repressive complex 2 (PRC2)–dependent histone H3 Lys-27 trimethylation activates HIF-mediated chemokine (C-X-C motif) receptor 4 (CXCR4) expression to promote invasion and metastasis”
From Hypoxic control of metastasis (2016) · cites this paper as [26]
Epigenetic modifications within prometastatic genes allow for enhanced expression of metastasis-associated HIF target genes.
“epigenetic modifications within prometastatic genes allow for enhanced expression of metastasis-associated HIF target genes”
From Hypoxic control of metastasis (2016) · cites this paper as [26]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364 · see citing works
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455 · see citing works
Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883 · see citing works
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717 · see citing works
Involvement of chemokine receptors in breast cancer metastasis
Müller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M. E., McClanahan, T., Murphy, E., Yuan, W., Wagner, S. N., et al. (2001) · Nature · doi:10.1038/35065016 · Cited by 5,340 · see citing works
Genome-wide maps of chromatin state in pluripotent and lineage-committed cells
Mikkelsen, T. S., Ku, M., Jaffe, D. B., Issac, B., Lieberman, E., Giannoukos, G., Alvarez, P., Brockman, W., Kim, T.-K., Koche, R. P., et al. (2007) · Nature · doi:10.1038/nature06008 · Cited by 4,129 · see citing works
The Polycomb complex PRC2 and its mark in life
Margueron, R., & Reinberg, D. (2011) · Nature · doi:10.1038/nature09784 · Cited by 3,347 · see citing works
Genes that mediate breast cancer metastasis to lung
Minn, A. J., Gupta, G. P., Siegel, P. M., Bos, P. D., Shu, W., Giri, D. D., Viale, A., Olshen, A. B., Gerald, W. L., & Massagué, J. (2005) · Nature · doi:10.1038/nature03799 · Cited by 2,922 · see citing works
Self-citationMetastasis: from dissemination to organ-specific colonization
Nguyen, D. X., Bos, P. D., & Massagué, J. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2622 · Cited by 2,637 · see citing works
Self-citationA multigenic program mediating breast cancer metastasis to bone
Kang, Y., Siegel, P. M., Shu, W., Drobnjak, M., Käkönen, S.-M., Cordon‐Cardo, C., Guise, T. A., & Massagué, J. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00132-6 · Cited by 2,562 · see citing works
Self-citationEvolving gene/transcript definitions significantly alter the interpretation of GeneChip data
Dai, M. (2005) · Nucleic Acids Research · doi:10.1093/nar/gni179 · Cited by 1,797 · see citing works
Mutations of the VHL tumour suppressor gene in renal carcinoma
Gnarra, J. R., Tory, K., Weng, Y., Schmidt, L., Wei, M. H., Li, H., Latif, F., Liu, S., Chen, F., Duh, F.-M., et al. (1994) · Nature Genetics · doi:10.1038/ng0594-85 · Cited by 1,730 · see citing works
Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma.
Herman, J. G., Latif, F., Weng, Y., Lerman, M. I., Zbar, B., Liu, S., Samid, D., Duan, D. S., Gnarra, J. R., & Linehan, W. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.9700 · Cited by 1,528 · see citing works
Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma
Varela, I., Tarpey, P. S., Raine, K. M., Huang, D., Ong, C. K., Stephens, P., Davies, H. R., Jones, D., Lin, M., Teague, J. W., et al. (2011) · Nature · doi:10.1038/nature09639 · Cited by 1,278 · see citing works
Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
Dalgliesh, G. L., Furge, K., Greenman, C., Chen, L., Bignell, G., Butler, A., Davies, H., Edkins, S., Hardy, C., Latimer, C., et al. (2010) · Nature · doi:10.1038/nature08672 · Cited by 1,173 · cited 2× · see citing works
“Mutations in epigenetic regulators make these genes attractive candidates as mediators of epigenetic remodeling in ccRCC 30,37 .”
Shen, X., Liu, Y., Hsu, Y.-J., Fujiwara, Y., Kim, J., Mao, X., Yuan, G.-C., & Orkin, S. H. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.10.016 · Cited by 1,021 · see citing works
Ezh1 and Ezh2 Maintain Repressive Chromatin through Different Mechanisms
Margueron, R., Li, G., Sarma, K., Blais, A., Zavadil, J., Woodcock, C. L. F., Dynlacht, B. D., & Reinberg, D. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.11.004 · Cited by 889 · see citing works
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 · see citing works
Metastatic patterns in adenocarcinoma
Hess, K. R., Varadhachary, G. R., Taylor, S. H., Wei, W., Raber, M. N., Lenzi, R., & Abbruzzese, J. L. (2006) · Cancer · doi:10.1002/cncr.21778 · Cited by 823 · see citing works
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 · see citing works
The von Hippel–Lindau tumour suppressor protein: O2 sensing and cancer
Kaelin, W. G. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2502 · Cited by 731 · see citing works
Latent Bone Metastasis in Breast Cancer Tied to Src-Dependent Survival Signals
Zhang, X. H.-F., Wang, Q., Gerald, W. L., Hudis, C. A., Norton, L., Smid, M., Foekens, J. A., & Massagué, J. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.05.017 · Cited by 663 · see citing works
Self-citationDNA Methylation of the First Exon Is Tightly Linked to Transcriptional Silencing
Brenet, F. A., Moh, M., Funk, P., Feierstein, E., Viale, A. J., Socci, N. D., & Scandura, J. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014524 · Cited by 627 · see citing works
Self-citationSong, L., & Crawford, G. E. (2010) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot5384 · Cited by 625 · see citing works
WNT/TCF Signaling through LEF1 and HOXB9 Mediates Lung Adenocarcinoma Metastasis
Nguyen, D. X., Chiang, A. C., Zhang, X. H.-F., Kim, J. Y., Kris, M. G., Ladanyi, M., Gerald, W. L., & Massagué, J. (2009) · Cell · doi:10.1016/j.cell.2009.04.030 · Cited by 622 · see citing works
Self-citationInhibition 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 · see citing works
Mole, D. R., Blancher, C., Copley, R. R., Pollard, P. J., Gleadle, J. M., Ragoussis, J., & Ratcliffe, P. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m901790200 · Cited by 552 · see citing works
HIF activation identifies early lesions in VHL kidneys
Mandriota, S. J., Turner, K. J., Davies, D. R., Murray, P. G., Morgan, N. V., Sowter, H. M., Wykoff, C. C., Maher, E. R., Harris, A. L., Ratcliffe, P. J., et al. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00071-5 · Cited by 483 · see citing works
Determinants and dynamics of genome accessibility
Bell, O., Tiwari, V. K., Thomä, N. H., & Schübeler, D. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3017 · Cited by 457 · see citing works
Genetic and Functional Studies Implicate <i>HIF1</i> α as a 14q Kidney Cancer Suppressor Gene
Shen, C., Beroukhim, R., Schumacher, S. E., Zhou, J., Chang, M., Signoretti, S., & Kaelin, W. G. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0098 · Cited by 413 · see citing works
Kaelin, W. G. (2006) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.2.010506.092049 · Cited by 335 · see citing works
Saharinen, J., Hyytiäinen, M. M., Taipale, J., & Keski‐Oja, J. (1999) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(99)00010-6 · Cited by 315 · see citing works
Ponomarev, V., Doubrovin, M., Serganova, I. S., Vider, J., Shavrin, A., Beresten, T., Ivanova, A. E., Ageyeva, L., Tourkova, V., Balatoni, J., et al. (2004) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-003-1441-5 · Cited by 286 · see citing works
Banks, R. E., Tirukonda, P. S., Taylor, C., Hornigold, N., Astuti, D., Cohen, D. R., Maher, E. R., Stanley, A. J., Harnden, P., Joyce, A., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3074 · Cited by 276 · see citing works
Zagzag, D., Krishnamachary, B., Yee, H. T., Okuyama, H., Chiriboga, L. A., Ali, M., Melamed, J., & Semenza, G. L. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4406 · Cited by 260 · see citing works
Yao, M. (2002) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/94.20.1569 · Cited by 244 · see citing works
Gene Expression Profiling Predicts Survival in Conventional Renal Cell Carcinoma
Zhao, H., Ljungberg, B., Grankvist, K., Rasmuson, T., Tibshirani, R. J., & Brooks, J. D. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0030013 · Cited by 227 · see citing works
Methods for assessing reproducibility of clustering patterns observed in analyses of microarray data
McShane, L. M., Radmacher, M. D., Freidlin, B., Yu, R., Li, M., & Simon, R. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.11.1462 · Cited by 210 · see citing works
Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling
Sonoshita, M., Aoki, M., Fuwa, H., Aoki, K., Hosogi, H., Sakai, Y., Hashida, H., Takabayashi, A., Sasaki, M., Robine, S., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.11.008 · Cited by 209 · see citing works
Young, A. C., Craven, R. A., Cohen, D. R., Taylor, C., Booth, C., Harnden, P., Cairns, D. A., Astuti, D., Gregory, W. M., Maher, E. R., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2131 · Cited by 174 · see citing works
A pipeline for the generation of shRNA transgenic mice
Dow, L. E., Premsrirut, P. K., Zuber, J., Fellmann, C., McJunkin, K., Miething, C., Park, Y., Dickins, R. A., Hannon, G. J., & Lowe, S. W. (2012) · Nature Protocols · doi:10.1038/nprot.2011.446 · Cited by 159 · see citing works
The VHL tumor suppressor and HIF: insights from genetic studies in mice
Kapitsinou, P. P., & Haase, V. H. (2008) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402313 · Cited by 151 · see citing works
Shi, J.-W., Wang, E., Zuber, J., Rappaport, A. R., Taylor, M. J., Johns, C., Lowe, S. W., & Vakoc, C. R. (2012) · Oncogene · doi:10.1038/onc.2012.110 · Cited by 120 · see citing works
Renal involvement in von Hippel-Lindau disease
Chauveau, D., Duvic, C., Chrétien, Y., Paraf, F., Droz, D., Melki, P. S., Hélénon, O., Richard, S., & Grünfeld, J. (1996) · Kidney International · doi:10.1038/ki.1996.395 · Cited by 119 · see citing works
Li, L., Zhang, L., Zhang, X., Yan, Q., Minamishima, Y. A., Olumi, A. F., Mao, M., Bartz, S. R., & Kaelin, W. G. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00282-07 · Cited by 108 · see citing works
Kashyap, V., Gudas, L. J., Brenet, F. A., Funk, P., Viale, A. J., & Scandura, J. M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.157545 · Cited by 98 · see citing works
Self-citationMcArthur, M., Gerum, S. E., & Stamatoyannopoulos, G. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4969 · Cited by 85 · see citing works
Montani, M., Heinimann, K., von Teichman, A., Rudolph, T. J., Perren, A. A., & Moch, H. (2010) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3181ddf54d · Cited by 74 · see citing works
In vitro cultivation of human renal cell cancer
Williams, R. D., Elliott, A. Y., Stein, N., & Fraley, E. E. (1976) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02797460 · Cited by 71 · see citing works
Boehm, T. L. J., Hofer, S., Winklehner, P., Kellersch, B., Geiger, C., Trockenbacher, A., Neyer, S., Fiegl, H., Ebner, S., Ivarsson, L., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg101 · Cited by 70 · see citing works
Differential role of CD133 and CXCR4 in renal cell carcinoma
D’Alterio, C., Cindolo, L., Portella, L., Polimeno, M., Consales, C., Riccio, A., Cioffi, M., Franco, R., Chiodini, P., Cartenì, G., et al. (2010) · Cell Cycle · doi:10.4161/cc.9.22.13680 · Cited by 67 · see citing works
In vitro cultivation of human renal cell cancer
Williams, R. D., Elliott, A. Y., Stein, N., & Fraley, E. E. (1978) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/bf02617972 · Cited by 54 · see citing works
Wang, L., Wang, L., Yang, B., Yang, Q., Qiao, S., Wang, Y., & Sun, Y. (2009) · Clinical & Experimental Metastasis · doi:10.1007/s10585-009-9294-3 · Cited by 48 · see citing works
Metastatic renal cell carcinoma: Results of a population-based study with 25 years follow-up
Schlesinger‐Raab, A., Treiber, U., Zaak, D., Hölzel, D., & Engel, J. (2008) · European Journal of Cancer · doi:10.1016/j.ejca.2008.07.039 · Cited by 40 · see citing works
Dendritic cells regulate T-cell deattachment through the integrin-interacting protein CYTIP
Hofer, S., Pfeil, K., Niederegger, H., Ebner, S., Nguyen, V. A., Kremmer, E., Auffinger, M., Neyer, S., Fürhapter, C., & Heufler, C. (2005) · Blood · doi:10.1182/blood-2005-01-0425 · Cited by 38 · see citing works
Watford, W. T., Li, D., Agnello, D., Durant, L. R., Yamaoka, K., Yao, Z. J., Ahn, H., Cheng, T. P., Hofmann, S. R., Cogliati, T., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02460-05 · Cited by 22 · see citing works
Chen, Q., Coffey, A., Bourgoin, S. G., & Gadina, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601629200 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Metastatic colonization by circulating tumour cells
Massagué, J., & Obenauf, A. C. (2016) · Nature · doi:10.1038/nature17038 · Cited by 2,062 · see citing works
Self-citationRankin, E. B., & Giaccia, A. J. (2016) · Science · doi:10.1126/science.aaf4405 · Cited by 1,340 · see citing works
Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth
Zhang, L., Zhang, S., Yao, J., Lowery, F. J., Zhang, Q., Huang, W.-C., Li, P., Li, M., Wang, X., Zhang, C., et al. (2015) · Nature · doi:10.1038/nature15376 · Cited by 1,080 · see citing works
Count-based differential expression analysis of RNA sequencing data using R and Bioconductor
Anders, S., McCarthy, D. J., Chen, Y., Okoniewski, M. J., Smyth, G. K., Huber, W. K., & Robinson, M. D. (2013) · Nature Protocols · doi:10.1038/nprot.2013.099 · Cited by 1,129 · see citing works
Ganesh, K., & Massagué, J. (2021) · Nature Medicine · doi:10.1038/s41591-020-01195-4 · Cited by 1,070 · see citing works
Self-citationCancer Stem Cells: Basic Concepts and Therapeutic Implications
Nassar, D., & Blanpain, C. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044438 · Cited by 869 · see citing works
Metabolic reprogramming and epigenetic modifications on the path to cancer
Sun, L., Zhang, H., & Gao, P. (2021) · Protein & Cell · doi:10.1007/s13238-021-00846-7 · Cited by 796 · see citing works
Groot, V. P., Rezaee, N., Wu, W., Cameron, J. L., Fishman, E. K., Hruban, R. H., Weiss, M. J., Zheng, L., Wolfgang, C. L., & He, J. (2018) · Annals of Surgery · doi:10.1097/sla.0000000000002234 · Cited by 757 · see citing works
Metastatic Stem Cells: Sources, Niches, and Vital Pathways
Óskarsson, T., Batlle, E., & Massagué, J. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.02.002 · Cited by 702 · see citing works
Self-citationThe Intricate Role of CXCR4 in Cancer
Chatterjee, S., Azad, B. B., & Nimmagadda, S. (2014) · Advances in cancer research · doi:10.1016/b978-0-12-411638-2.00002-1 · Cited by 674 · see citing works
Surviving at a Distance: Organ-Specific Metastasis
Obenauf, A. C., & Massagué, J. (2015) · Trends in cancer · doi:10.1016/j.trecan.2015.07.009 · Cited by 569 · see citing works
Self-citationVanharanta, S., & Massagué, J. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.09.007 · Cited by 563 · see citing works
Self-citationHypoxia-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 507 · see citing works
On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models
Cho, H., Du, X., Rizzi, J. P., Liberzon, E., Chakraborty, A. A., Gao, W., Carvo, I., Signoretti, S., Bruick, R. K., Josey, J. A., et al. (2016) · Nature · doi:10.1038/nature19795 · Cited by 451 · see citing works
Gan, L., Yang, Y., Li, Q., Feng, Y., Liu, T., & Guo, W.-J. (2018) · Biomarker Research · doi:10.1186/s40364-018-0122-2 · Cited by 428 · see citing works
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 411 · see citing works
Gaude, E., & Frezza, C. (2016) · Nature Communications · doi:10.1038/ncomms13041 · Cited by 366 · see citing works
Metastasis-Initiating Cells and Ecosystems
Massagué, J., & Ganesh, K. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0010 · Cited by 372 · see citing works
Self-citationNfib Promotes Metastasis through a Widespread Increase in Chromatin Accessibility
Denny, S. K., Yang, D., Chuang, C.-H., Brady Jennifer, J., Lim, J. S., Grüner, B. M., Chiou, S., Schep, A. N., Baral, J., Hamard, C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.05.052 · Cited by 358 · see citing works
Epithelial–mesenchymal transition: a new target in anticancer drug discovery
Marcucci, F., Stassi, G., & Maria, R. D. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.13 · Cited by 340 · see citing works
- Self-citation
Direct 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 · see citing works
Cancer, Oxidative Stress, and MetastasisPreprint
Gill, J. G., Piskounova, E., & Morrison, S. J. (2016) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2016.81.030791 · Cited by 269 · see citing works
Interplay between epigenetics and metabolism in oncogenesis: mechanisms and therapeutic approaches
Wong, C. C., Qian, Y., & Yu, J. Q. (2017) · Oncogene · doi:10.1038/onc.2016.485 · Cited by 260 · see citing works
Targeting Breast Cancer Metastasis
Jin, X., & Mu, P. (2015) · Breast Cancer Basic and Clinical Research · doi:10.4137/bcbcr.s25460 · Cited by 239 · see citing works
Mennerich, D., Kubaichuk, K. I., & Kietzmann, T. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.08.005 · Cited by 232 · see citing works
Chronic inflammation, cancer development and immunotherapy
Wen, Y., Zhu, Y., Zhang, C., Yang, X., Gao, Y., Li, M., Yang, H., Liu, T., & Tang, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1040163 · Cited by 231 · see citing works
Hallmarks of cancer—the new testament
Senga, S. S., & Grose, R. P. (2021) · Open Biology · doi:10.1098/rsob.200358 · Cited by 221 · see citing works
A Clearer View of the Molecular Complexity of Clear Cell Renal Cell Carcinoma
Frew, I. J., & Moch, H. (2014) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012414-040306 · Cited by 224 · see citing works
Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients
Fendler, A., Bauer, D. E., Busch, J. F., Jung, K., Wulf-Goldenberg, A., Kunz, S., Song, K., Myszczyszyn, A., Elezkurtaj, S., Erguen, B., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14700-7 · Cited by 190 · see citing works
The Epigenetic Hallmarks of Cancer
Esteller, M., Dawson, M. A., Kadoch, C., Rassool, F. V., Jones, P. A., & Baylin, S. B. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0296 · Cited by 184 · see citing works
VHL Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma
Yao, X., Tan, J. Y., Lim, K. J., Koh, J., Ooi, W. F., Li, Z., Huang, D., Xing, M., Chan, Y. S., Qu, J. Z., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0375 · Cited by 166 · see citing works
Genetic and metabolic hallmarks of clear cell renal cell carcinoma
Sanchez, D. J., & Simon, M. C. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.06.003 · Cited by 160 · see citing works
Redox Imbalance and Biochemical Changes in Cancer
Jorgenson, T. C., Zhong, W., & Oberley, T. D. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-1117 · Cited by 158 · see citing works
Peng, S.-B., Zhang, X., Paul, D. C., Kays, L. M., Gough, W. H., Stewart, J. A., Uhlik, M. T., Chen, Q., Hui, Y., Zamek‐Gliszczynski, M. J., et al. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0850 · Cited by 149 · see citing works
Causal integration of multi‐omics data with prior knowledge to generate mechanistic hypotheses
Dugourd, A., Kuppe, C., Sciacovelli, M., Gjerga, E., Gabor, A., Emdal, K. B., Vieira, V., Bekker‐Jensen, D. B., Kranz, J., Bindels, E. M. J., et al. (2021) · Molecular Systems Biology · doi:10.15252/msb.20209730 · Cited by 149 · see citing works
Evolving cancer–niche interactions and therapeutic targets during bone metastasis
Satcher, R. L., & Zhang, X. H.-F. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00406-5 · Cited by 147 · see citing works
Vanharanta, S., Marney, C. B., Shu, W., Valiente, M., Zou, Y., Mele, A., Darnell, R. B., & Massagué, J. (2014) · eLife · doi:10.7554/elife.02734 · Cited by 143 · see citing works
Self-citationEpigenetic remodelling shapes inflammatory renal cancer and neutrophil-dependent metastasis
Nishida, J., Momoi, Y., Miyakuni, K., Tamura, Y., Takahashi, K., Koinuma, D., Miyazono, K., & Ehata, S. (2020) · Nature Cell Biology · doi:10.1038/s41556-020-0491-2 · Cited by 135 · see citing works
Gatto, F., Nookaew, I., & Nielsen, J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1319196111 · Cited by 132 · see citing works
Genomic insights into cancer-associated aberrant CpG island hypermethylation
Sproul, D., & Meehan, R. R. (2013) · Briefings in Functional Genomics · doi:10.1093/bfgp/els063 · Cited by 130 · see citing works
Redox Regulation in Cancer Cells during Metastasis
Tasdogan, A., Ubellacker, J. M., & Morrison, S. J. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0558 · Cited by 123 · see citing works
Metabolism and Epigenetic Interplay in Cancer: Regulation and Putative Therapeutic Targets
Miranda‐Gonçalves, V., Lameirinhas, A., Henrique, R., & Jerónimo, C. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00427 · Cited by 122 · see citing works
Epigenetic crosstalk between hypoxia and tumor driven by HIF regulation
Li, T., Mao, C., Wang, X., Shi, Y., & Tao, Y. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01733-5 · Cited by 125 · see citing works
Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis
Pavlović, M., Estape, A. A., Rojo, F., Bellmunt, A., Tarragona, M., Guiu, M., Planet, E., García‐Albéniz, X., Morales, M. L. G., Urosevic, J., et al. (2015) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv256 · Cited by 113 · see citing works
Epigenetic regulation in cancer
Gu, M., Ren, B., Fang, Y., Ren, J., Liu, X., Wang, X., Zhou, F., Xiao, R., Luo, X., You, L., et al. (2024) · MedComm · doi:10.1002/mco2.495 · Cited by 119 · see citing works
Pancancer analysis of DNA methylation-driven genes using MethylMix
Gevaert, O., Tibshirani, R. J., & Plevritis, S. K. (2015) · Genome biology · doi:10.1186/s13059-014-0579-8 · Cited by 114 · see citing works
Li, F., Aljahdali, I. A. M., Zhang, R., Nastiuk, K. L., Krolewski, J. J., & Ling, X. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02026-1 · Cited by 113 · see citing works
Role of DNA methylation in renal cell carcinoma
Shenoy, N. K., Vallumsetla, N., Zou, Y., Galeas, J. N., Shrivastava, M. S., Hu, C. H., Suszták, K., & Verma, A. (2015) · Journal of Hematology & Oncology · doi:10.1186/s13045-015-0180-y · Cited by 104 · see citing works
EZH2 in Cancer Progression and Potential Application in Cancer Therapy: A Friend or Foe?
Yan, K.-S., Lin, C., Liao, T.-W., Peng, C.-M., Lee, S.-C., Liu, Y., Chan, W. P., & Chou, R. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061172 · Cited by 97 · see citing works
The multifaceted von Hippel–Lindau tumour suppressor protein
Robinson, C. M., & Ohh, M. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.02.026 · Cited by 96 · see citing works
A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma
Syafruddin, S. E., Rodrigues, P., Vojtasova, E., Patel, S. A., Zaini, M. N., Burge, J., Warren, A. Y., Stewart, G. D., Eisen, T. G., Bihary, D., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09116-x · Cited by 95 · see citing works
Self-citationLiu, L., Xu, Z., Zhong, L., Wang, H., Jiang, S., Long, Q., Xu, J., & Guo, J. (2014) · British Journal of Urology · doi:10.1111/bju.12702 · Cited by 91 · see citing works
Cancer Evolution: A Multifaceted Affair
Ciriello, G., Magnani, L., Aitken, S. J., Akkari, L., Behjati, S., Hanahan, D., Landau, D. A., López-Bigas, N., Lupiáñez, D. G., Marine, J., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0530 · Cited by 89 · see citing works
Self-citationMahara, S., Lee, P. L., Feng, M., Tergaonkar, V., Chng, W. J., & Yu, Q. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1602079113 · Cited by 87 · see citing works
Evolving concepts of tumor heterogeneity
Zellmer, V. R., & Zhang, S. (2014) · Cell & Bioscience · doi:10.1186/2045-3701-4-69 · Cited by 87 · see citing works
Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesisPreprint
Wassef, M. A., Rodilla, V., Teissandier, A., Zeitouni, B., Gruel, N., Sadacca, B., Irondelle, M., Charruel, M., Ducos, B., Michaud, A., et al. (2015) · Genes & Development · doi:10.1101/gad.269522.115 · Cited by 86 · see citing works
Autophagy mediates HIF2α degradation and suppresses renal tumorigenesis
Liu, X.-D., Yao, J., Tripathi, D. N., Ding, Z., Xu, Y., Sun, M., Zhang, J., Bai, S., Germán, P., Hoang, A. G., et al. (2014) · Oncogene · doi:10.1038/onc.2014.199 · Cited by 86 · see citing works
Grampp, S., Platt, J. L., Lauer, V., Salama, R. A., Kranz, F., Neumann, V. K., Wach, S., Stöhr, C., Hartmann, A., Eckardt, K., et al. (2016) · Nature Communications · doi:10.1038/ncomms13183 · Cited by 86 · see citing works
The roles of epigenetics in cancer progression and metastasis
Chen, J. F.-Y., & Yan, Q. (2021) · Biochemical Journal · doi:10.1042/bcj20210084 · Cited by 88 · see citing works
Shenoy, N. K., & Pagliaro, L. C. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw241 · Cited by 86 · see citing works
Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma
Hu, J., Tan, P., Ishihara, M., Bayley, N. A., Schokrpur, S., Reynoso, J. G., Zhang, Y., Lim, R. J., Dumitras, C., Yang, L., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01362-2 · Cited by 85 · see citing works
Underlying Causes and Therapeutic Targeting of the Inflammatory Tumor Microenvironment
Comen, E. A., Bowman, R. L., & Kleppe, M. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00056 · Cited by 84 · see citing works
The renal lineage factor PAX8 controls oncogenic signalling in kidney cancer
Patel, S. A., Hirosue, S., Rodrigues, P., Vojtasova, E., Richardson, E. K., Ge, J., Syafruddin, S. E., Speed, A., Papachristou, E. K., Baker, D., et al. (2022) · Nature · doi:10.1038/s41586-022-04809-8 · Cited by 83 · see citing works
Self-citationTreatment strategies for clear cell renal cell carcinoma: Past, present and future
Yang, J., Wang, K., & Yang, Z. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1133832 · Cited by 85 · see citing works
Molecular aberrations, targeted therapy, and renal cell carcinoma: current state-of-the-art
Randall, J. M., Millard, F. E., & Kurzrock, R. (2014) · Cancer and Metastasis Reviews · doi:10.1007/s10555-014-9533-1 · Cited by 81 · see citing works
Nishida, J., Miyazono, K., & Ehata, S. (2018) · Oncogene · doi:10.1038/s41388-017-0084-0 · Cited by 78 · see citing works
D’Anna, F., Dyck, L. V., Xiong, J., Zhao, H., Berrens, R. V., Qian, J., Bieniasz-Krzywiec, P., Chandra, V., Schoonjans, L., Matthews, J. B., et al. (2020) · Genome biology · doi:10.1186/s13059-020-02087-z · Cited by 75 · see citing works
Bone as a Preferential Site for Metastasis
Sowder, M. E., & Johnson, R. W. (2018) · JBMR Plus · doi:10.1002/jbm4.10126 · Cited by 73 · see citing works
Pathomechanisms: homeostatic chemokines in health, tissue regeneration, and progressive diseases
Anders, H., Romagnani, P., & Mantovani, A. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2013.12.002 · Cited by 74 · see citing works
ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma
Green, Y. S., Ferreira dos Santos, M. C., Fuja, D. G., Reichert, E. C., Campos, A. R., Cowman, S. J., Acuña Pilarte, K., Kohan, J., Tripp, S. R., Leibold, E. A., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02460-1 · Cited by 69 · see citing works
CD49f-positive cell population efficiently enriches colon cancer-initiating cells
Haraguchi, N., Ishii, H., Mimori, K., Ohta, K., Uemura, M., Nishimura, J., Hata, T., Takemasa, I., Mizushima, T., Yamamoto, H., et al. (2013) · International Journal of Oncology · doi:10.3892/ijo.2013.1955 · Cited by 69 · see citing works
Kurashige, J., Hasegawa, T., Niida, A., Sugimachi, K., Deng, N., Mima, K., Uchi, R., Sawada, G., Takahashi, Y., Eguchi, H., et al. (2016) · Scientific Reports · doi:10.1038/srep22371 · Cited by 69 · see citing works
Predictive biomarkers in renal cell cancer: Insights in drug resistance mechanisms
van der Mijn, J. C., Mier, J. W., Broxterman, H. J., & Verheul, H. M. W. (2014) · Drug Resistance Updates · doi:10.1016/j.drup.2014.10.003 · Cited by 68 · see citing works
Ma, X., Gu, L., Li, H., Gao, Y., Li, X., Shen, D., Gong, H., Li, S., Niu, S., Zhang, Y., et al. (2015) · Journal of Translational Medicine · doi:10.1186/s12967-015-0421-4 · Cited by 66 · see citing works
Metabolic Dysregulations and Epigenetics: A Bidirectional Interplay that Drives Tumor Progression
Crispo, F., Condelli, V., Lepore, S., Notarangelo, T., Sgambato, A., Esposito, F., Maddalena, F., & Landriscina, M. (2019) · Cells · doi:10.3390/cells8080798 · Cited by 61 · see citing works
Dynamic reprogramming of DNA methylation in SETD2-deregulated renal cell carcinoma
Tiedemann, R. L., Hlady, R. A., Hanavan, P. D., Lake, D. F., Tibes, R., Lee, J., Choi, J.-H., Ho, T. H., & Robertson, K. D. (2015) · Oncotarget · doi:10.18632/oncotarget.6481 · Cited by 63 · see citing works
Patel, S. A., Rodrigues, P., Wesolowski, L., & Vanharanta, S. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-01127-6 · Cited by 58 · see citing works
Self-citationLachance, G., Uniacke, J., Audas, T. E., Holterman, C. E., Franovic, A., Payette, J., & Lee, S. B. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322909111 · Cited by 61 · see citing works
Jacob, L. S., Vanharanta, S., Obenauf, A. C., Pirun, M., Viale, A. J., Socci, N. D., & Massagué, J. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-0562 · Cited by 59 · see citing works
Self-citationSciacovelli, M., Dugourd, A. J. F., Valcárcel-Jiménez, L., Yang, M. H., Nikitopoulou, E., Costa, A. S. H., Tronci, L., Caraffini, V., Rodrigues, P., Schmidt, C., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-35036-4 · Cited by 60 · see citing works
Self-citationEpigenetic determinants of metastasis
Patel, S. A., & Vanharanta, S. (2016) · Molecular Oncology · doi:10.1016/j.molonc.2016.09.008 · Cited by 56 · see citing works
Self-citationFandrey, J., Schödel, J., Eckardt, K., Katschinski, D. M., & Wenger, R. H. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-019-02334-8 · Cited by 54 · see citing works
Targeting HIF2 in Clear Cell Renal Cell CarcinomaPreprint
Cho, H., & Kaelin, W. G. (2016) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2016.81.030833 · Cited by 56 · see citing works
Peters, I., Dubrowinskaja, N., Abbas, M., Seidel, C. A., Kogosov, M., Scherer, R., Gebauer, K., Merseburger, A. S., Kuczyk, M. A., Grünwald, V., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0091440 · Cited by 54 · see citing works
Xu, G., Lou, N., Shi, H., Xu, Y., Ruan, H., Xiao, W., Liu, L., Li, X., Xiao, H., Qiu, B., et al. (2018) · BMC Cancer · doi:10.1186/s12885-017-3761-z · Cited by 54 · see citing works
NF-κB–Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis
Rodrigues, P., Patel, S. A., Harewood, L., Olan, I., Vojtasova, E., Syafruddin, S. E., Zaini, M. N., Richardson, E. K., Burge, J., Warren, A. Y., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1211 · Cited by 53 · see citing works
Self-citationVHL promotes immune response against renal cell carcinoma via NF-κB–dependent regulation of VCAM-1
Labrousse-Arias, D., Martínez‐Alonso, E., Corral-Escariz, M., Bienes-Martínez, R., Berridy, J., Serrano‐Oviedo, L., Conde, E., García‐Bermejo, L., Bachs, J. M. G., Sánchez, A. S. S., et al. (2017) · The Journal of Cell Biology · doi:10.1083/jcb.201608024 · Cited by 53 · see citing works
Iqbal, W., Alkarim, S., Al-Hejin, A. M., Mukhtar, H., & Saini, K. S. (2016) · Oncotarget · doi:10.18632/oncotarget.10942 · Cited by 49 · see citing works
Pharmacological HIF2α inhibition improves VHL disease–associated phenotypes in zebrafish model
Metelo, A. M., Noonan, H. R., Li, X., Jin, Y. N., Baker, R., Kamentsky, L. D., Zhang, Y., van Rooijen, E., Shin, J. T., Carpenter, A. E., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73665 · Cited by 49 · see citing works
Dubrowinskaja, N., Gebauer, K., Peters, I., Hennenlotter, J., Abbas, M., Scherer, R., Tezval, H., Merseburger, A. S., Stenzl, A., Grünwald, V., et al. (2014) · Cancer Medicine · doi:10.1002/cam4.181 · Cited by 49 · see citing works
Winter, S., Fisel, P., Büttner, F., Rausch, S., D’Amico, D., Hennenlotter, J., Kruck, S., Nies, A. T., Stenzl, A., Junker, K., et al. (2016) · Scientific Reports · doi:10.1038/srep29930 · Cited by 47 · see citing works
Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis
Nam, H., Chandrashekar, D. S., Kundu, A., Shelar, S. B., Kho, E.-Y., Sonpavde, G., Naik, G., Ghatalia, P., Livi, C. B., Varambally, S., et al. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-17-0636 · Cited by 46 · see citing works
Prominent Role of Histone Modifications in the Regulation of Tumor Metastasis
Markouli, M., Strepkos, D., Basdra, E. K., Papavassiliou, A. G., & Piperi, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052778 · Cited by 45 · see citing works
PRDM16 suppresses HIF-targeted gene expression in kidney cancer
Kundu, A., Nam, H., Shelar, S. B., Chandrashekar, D. S., Brinkley, G. J., Karki, S., Mitchell, T., Livi, C. B., Buckhaults, P., Kirkman, R. L., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20191005 · Cited by 43 · see citing works
Richter, S., Qin, N., Pacak, K., & Eisenhofer, G. (2013) · Advances in Pharmacology · doi:10.1016/b978-0-12-411512-5.00014-2 · Cited by 42 · see citing works
Hlady, R. A., Zhou, D., Puszyk, W. M., Roberts, L. R., Liu, C., & Robertson, K. D. (2017) · Epigenetics · doi:10.1080/15592294.2016.1277297 · Cited by 39 · see citing works
Sakaguchi, T., Yoshino, H., Sugita, S., Miyamoto, K., Yonemori, M., Osako, Y., Meguro‐Horike, M., Horike, S., Nakagawa, M., & Enokida, H. (2018) · Oncotarget · doi:10.18632/oncotarget.25190 · Cited by 38 · see citing works
Cancer Cells Hijack PRC2 to Modify Multiple Cytokine Pathways
Hassan, M. A. E., Huang, K., Eswara, M. B. K., Zhao, M., Lan, S., Tao, Y., Liu, Y., Liu, J., McCurdy, S. R., Ma, A., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126466 · Cited by 38 · see citing works
Marech, I., Gadaleta, C. D., & Ranieri, G. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms150713060 · Cited by 37 · see citing works
- Authors
- Vanharanta, S., Shu, W., Brenet, F., Hakimi, A. A., Heguy, A., Viale, A., Reuter, V. E., Hsieh, J. J.-D., Scandura, J. M., & Massagué, J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Weill Cornell Medicine (US)
- Corresponding author
- Massagué, Joan
- ORCID
- Venue
- Nature Medicine
- Published
- 2012-12-09
- Volume
- 19
- Issue
- 1
- Pages
- 50-56
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC3540187
- OpenAlex
- W2086553719
- Cited by
- 215
- References
- 57
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 6 · 2023: 11 · 2022: 21 · 2021: 19 · 2020: 13 · 2019: 13 · 2018: 14 · 2017: 12 · 2016: 23 · 2015: 22 · 2014: 29 · 2013: 14 · 2012: 1
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- National Cancer Institute (P01CA129243, P30CA008748, T32CA082088)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- clear cell renal cell carcinoma, VHL, hypoxia-inducible factor, metastasis, epigenetic reprogramming, CXCR4, H3K27me3, polycomb repressive complex 2, DNA methylation, chromatin modification, tumor progression, chemotaxis, cytokine resistance, multiple organ metastasis
- MeSH terms
- Animals, Base Sequence, Carcinoma, Renal Cell, Histones, Humans, Kidney Neoplasms, Neoplasm Metastasis, Transcription Factors, Gene Expression Regulation, Neoplastic, Mice, SCID, Mice, Inbred NOD, Sequence Analysis, DNA, DNA Methylation, Receptors, CXCR4, Cell Line, Tumor, Mice, Hypoxia-Inducible Factor 1, Von Hippel-Lindau Tumor Suppressor Protein, Polycomb Repressive Complex 2
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
