O-GlcNAcylation of FOXK1 orchestrates the E2F pathway and promotes oncogenesis
Open accessPreprint — published as 10.1038/s41467-025-61022-7
Abstract
Gene transcription is a highly regulated process, and deregulation of transcription factors activity underlies numerous pathologies including cancer. Albeit near four decades of studies have established that the E2F pathway is a core transcriptional network that govern cell division in multi-cellular organisms 1,2 , the molecular mechanisms that underlie the functions of E2F transcription factors remain incompletely understood. FOXK1 and FOXK2 transcription factors have recently emerged as important regulators of cell metabolism, autophagy and cell differentiation 3–6 . While both FOXK1 and FOXK2 interact with the histone H2AK119ub deubiquitinase BAP1 and possess many overlapping functions in normal biology, their specific functions as well as deregulation of their transcriptional activity in cancer is less clear and sometimes contradictory 7–13 . Here, we show that elevated expression of FOXK1, but not FOXK2, in primary normal cells promotes transcription of E2F target genes associated with increased proliferation and delayed entry into cellular senescence. FOXK1 expressing cells are highly prone to cellular transformation revealing important oncogenic properties of FOXK1 in tumor initiation. High expression of FOXK1 in patient tumors is also highly correlated with E2F gene expression. Mechanistically, we demonstrate that FOXK1, but not FOXK2, is specifically modified by O-GlcNAcylation. FOXK1 O-GlcNAcylation is modulated during the cell cycle with the highest levels occurring during the time of E2F pathway activation at G1/S. Moreover, loss of FOXK1 O-GlcNAcylation impairs FOXK1 ability to promote cell proliferation, cellular transformation and tumor growth. Mechanistically, expression of FOXK1 O-GlcNAcylation-defective mutants results in reduced recruitment of BAP1 to gene regulatory regions. This event is associated with a concomitant increase in the levels of histone H2AK119ub and a decrease in the levels of H3K4me1, resulting in a transcriptional repressive chromatin environment. Our results define an essential role of O-GlcNAcylation in modulating the functions of FOXK1 in controlling the cell cycle of normal and cancer cells through orchestration of the E2F pathway.
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Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890 · see citing works
NIH Image to ImageJ: 25 years of image analysis
Schneider, C. A., Rasband, W. S., & Eliceiri, K. W. (2012) · Nature Methods · doi:10.1038/nmeth.2089 · Cited by 64,638 · see citing works
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219 · see citing works
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464 · see citing works
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386 · 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
Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal
Gao, J., Aksoy, B. A., Dogrusoz, U., Dresdner, G., Gross, B., Sumer, S. O., Sun, Y., Jacobsen, A., Sinha, R., Larsson, E., et al. (2013) · Science Signaling · doi:10.1126/scisignal.2004088 · Cited by 15,160 · see citing works
Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y. C., Laslo, P., Cheng, J. X., Murre, C., Singh, H., & Glass, C. K. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.05.004 · Cited by 13,382 · see citing works
Enrichr: a comprehensive gene set enrichment analysis web server 2016 update
Kuleshov, M. V., Jones, M. R., Rouillard, A. D., Fernandez, N. F., Duan, Q., Wang, Z., Koplev, S., Jenkins, S. L., Jagodnik, K. M., Lachmann, A., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw377 · Cited by 10,799 · see citing works
Hallmarks of Cancer: New Dimensions
Hanahan, D. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1059 · Cited by 9,887 · see citing works
UCSF ChimeraX : Structure visualization for researchers, educators, and developers
Pettersen, E. F., Goddard, T. D., Huang, C. C., Meng, E. C., Couch, G. S., Croll, T. I., Morris, J. H., & Ferrin, T. E. (2020) · Protein Science · doi:10.1002/pro.3943 · Cited by 9,327 · see citing works
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
Rao, S. S. P., Huntley, M. H., Durand, N. C., Stamenova, E. K., Bochkov, I. D., Robinson, J. T., Sanborn, A. L., Machol, I., Omer, A. D., Lander, E. S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.11.021 · Cited by 9,212 · see citing works
deepTools2: a next generation web server for deep-sequencing data analysis
Ramírez, F., Ryan, D. P., Grüning, B., Bhardwaj, V., Kilpert, F., Richter, A. S., Heyne, S., Dündar, F., & Manke, T. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw257 · Cited by 8,096 · see citing works
Varadi, M., Anyango, S., Deshpande, M., Nair, S., Natassia, C., Yordanova, G., Yuan, D., Stroe, O., Wood, G., Laydon, A., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab1061 · Cited by 7,850 · see citing works
Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool
Chen, E. Y., Tan, C. M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G. V., Clark, N. R., & Ma’ayan, A. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-128 · Cited by 7,814 · see citing works
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · see citing works
Visualizing and interpreting cancer genomics data via the Xena platform
Goldman, M. J., Craft, B., Hastie, M., Repečka, K., McDade, F., Kamath, A., Banerjee, A., Luo, Y., Rogers, D., Brooks, A. N., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0546-8 · Cited by 4,481 · see citing works
TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data
Colaprico, A., Silva, T. C., Olsen, C., Garofano, L., Cava, C., Garolini, D., Sabedot, T. S., Malta, T. M., Pagnotta, S. M., Castiglioni, I., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1507 · Cited by 4,137 · see citing works
The nf-core framework for community-curated bioinformatics pipelines
Ewels, P., Peltzer, A., Fillinger, S., Patel, H., Alneberg, J., Wilm, A., Garcia, M., Tommaso, P. D., & Nahnsen, S. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0439-x · Cited by 4,028 · see citing works
Gene set knowledge discovery with enrichr
Xie, Z., Bailey, A., Kuleshov, M. V., Clarke, D. J. B., Evangelista, J. E., Jenkins, S. L., Lachmann, A., Wojciechowicz, M. L., Kropiwnicki, E., Jagodnik, K. M., et al. (2021) · Current Protocols · doi:10.1002/cpz1.90 · Cited by 3,451 · see citing works
Defining a Cancer Dependency Map
Tsherniak, A., Vazquez, F., Montgomery, P. G., Weir, B. A., Kryukov, G., Cowley, G. S., Gill, S., Harrington, W. F., Pantel, S., Krill-Burger, J. M., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.010 · Cited by 3,276 · see citing works
Pan-cancer analysis of whole genomes
The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, Aaltonen, L. A., Abascal, F., Abeshouse, A., Aburatani, H., Adams, D. J., Agrawal, N., Ahn, K. S., Ahn, S.-M., Aikata, H., et al. (2020) · Nature · doi:10.1038/s41586-020-1969-6 · Cited by 3,064 · see citing works
Matthews, H. K., Bertoli, C., & de Bruin, R. A. M. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00404-3 · Cited by 1,506 · see citing works
Fry, D. W., Harvey, P. J., Keller, P. R., Elliott, W. L., Meade, M., Trachet, E., Albassam, M., Zheng, X., Leopold, W. R., Pryer, N. K., et al. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.1427.3.11 · Cited by 1,236 · see citing works
GSEApy: a comprehensive package for performing gene set enrichment analysis in Python
Fang, Z., Liu, X., & Peltz, G. (2022) · Bioinformatics · doi:10.1093/bioinformatics/btac757 · Cited by 1,209 · see citing works
Protein O-GlcNAcylation: emerging mechanisms and functions
Yang, X., & Qian, K. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.22 · Cited by 1,203 · see citing works
Martin, F. J., Amode, M. R., Aneja, A., Austine-Orimoloye, O., Azov, A. G., Barnes, I., Becker, A., Bennett, R., Berry, A. E., Bhai, J. N. N. T., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac958 · Cited by 980 · see citing works
High-resolution TADs reveal DNA sequences underlying genome organization in flies
Ramírez, F., Bhardwaj, V., Arrigoni, L., Lam, K. C., Grüning, B. A., Villaveces, J. M., Habermann, B. H., Akhtar, A., & Manke, T. (2018) · Nature Communications · doi:10.1038/s41467-017-02525-w · Cited by 974 · see citing works
de Bruijn, I., Kundra, R., Mastrogiacomo, B., Tran, T. N., Sikina, L., Mazor, T., Li, X., Ochoa, A., Zhao, G., Lai, B., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-23-0816 · Cited by 886 · see citing works
PML regulates p53 acetylation and premature senescence induced by oncogenic Ras
Pearson, M. A., Carbone, R., Sebastiani, C., Cioce, M., Fagioli, M., Saito, S., Higashimoto, Y., Appella, E., Minucci, S., Pandolfi, P. P., et al. (2000) · Nature · doi:10.1038/35018127 · Cited by 838 · see citing works
The broken cycle: E2F dysfunction in cancer
Kent, L. N., & Leone, G. W. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0143-7 · Cited by 786 · see citing works
Phosphofructokinase 1 Glycosylation Regulates Cell Growth and Metabolism
Yi, W., Clark, P. M., Mason, D. E., Keenan, M. C., Hill, C., Goddard, W. A., Peters, E. C., Driggers, E. M., & Hsieh‐Wilson, L. C. (2012) · Science · doi:10.1126/science.1222278 · Cited by 680 · see citing works
A novel role for high-mobility group A proteins in cellular senescence and heterochromatin formation
Narita, M., Narita, M., Krizhanovsky, V., Nuñez, S., Chicas, A., Hearn, S. A., Myers, M. P., & Lowe, S. W. (2006) · Cell · doi:10.1016/j.cell.2006.05.052 · Cited by 629 · see citing works
UCSF ChimeraX : Structure Visualization for Researchers, Educators, and Developers
Pettersen, E. F., Goddard, T. D., Huang, C. C., Meng, E. C., Couch, G. S., Croll, T. I., Morris, J. H., & Ferrin, T. E. (2020) · Apollo (University of Cambridge) · doi:10.17863/cam.57077 · Cited by 617 · see citing works
Peak calling by Sparse Enrichment Analysis for CUT&RUN chromatin profiling
Meers, M. P., Tenenbaum, D., & Henikoff, S. (2019) · Epigenetics & Chromatin · doi:10.1186/s13072-019-0287-4 · Cited by 556 · see citing works
PML is induced by oncogenic <i>ras</i> and promotes premature senescence
Ferbeyre, G., de Stanchina, E., Querido, E., Baptiste, N., Prives, C., & Lowe, S. W. (2000) · Genes & Development · doi:10.1101/gad.14.16.2015 · Cited by 536 · see citing works
Durocher, D., Taylor, I., Sarbassova, D., Haire, L., Westcott, S., Jackson, S., Smerdon, S., & Yaffe, M. (2000) · Molecules and Cells · doi:10.1016/s1097-2765(00)00114-3 · Cited by 475 · see citing works
O-GlcNAc signalling: implications for cancer cell biology
Slawson, C. M., & Hart, G. W. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3114 · Cited by 459 · see citing works
Hu, D., Gao, X., Morgan, M. A., Herz, H.-M., Smith, E. R., & Shilatifard, A. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01181-13 · Cited by 439 · see citing works
BRD4 Connects Enhancer Remodeling to Senescence Immune Surveillance
Tasdemir, N., Banito, A., Roe, J.-S., Alonso-Curbelo, D., Camiolo, M., Tschaharganeh, D. F., Huang, C.-H., Aksoy, O., Bolden, J. E., Chen, C.-C., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0217 · Cited by 415 · see citing works
Mitochondrial Dysfunction Contributes to Oncogene-Induced Senescence
Moiseeva, O., Bourdeau, V., Roux, A., Deschênes-Simard, X., & Ferbeyre, G. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01868-08 · Cited by 408 · see citing works
The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence
Mallette, F. A., Gaumont-Leclerc, M.-F., & Ferbeyre, G. (2007) · Genes & Development · doi:10.1101/gad.1487307 · Cited by 406 · see citing works
E2F – at the crossroads of life and death
Polager, S., & Ginsberg, D. (2008) · Trends in Cell Biology · doi:10.1016/j.tcb.2008.08.003 · Cited by 300 · see citing works
Lynch, T. P., Ferrer, C. M., Jackson, S. R., Shahriari, K. S., Vosseller, K., & Reginato, M. J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.302547 · Cited by 286 · see citing works
The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1
Machida, Y. J., Machida, Y., Vashisht, A. A., Wohlschlegel, J. A., & Dutta, A. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.046755 · Cited by 274 · see citing works
Yu, H., Mashtalir, N., Daou, S., Hammond-Martel, I., Ross, J., Sui, G., Hart, G. W., Rauscher, F. J., Drobetsky, E. A., Milot, É., et al. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00396-10 · Cited by 273 · see citing works
Self-citationMesothelioma patients with germline BAP1 mutations have 7-fold improved long-term survival
Baumann, F., Flores, E. G., Napolitano, A., Kanodia, S., Taioli, E., Pass, H. I., Yang, H., & Carbone, M. (2014) · Carcinogenesis · doi:10.1093/carcin/bgu227 · Cited by 255 · see citing works
Coordinating gene expression during the cell cycle
Fischer, M., Schade, A. E., Branigan, T. B., Müller, G. A., & DeCaprio, J. A. (2022) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2022.06.007 · Cited by 218 · see citing works
BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5
Qin, J., Zhou, Z., Chen, W., Wang, C., Zhang, H., Ge, G., Shao, M., You, D., Fan, Z., Xia, H., et al. (2015) · Nature Communications · doi:10.1038/ncomms9471 · Cited by 215 · see citing works
Mashtalir, N., Daou, S., Barbour, H., Nkwe, N. S., Gagnon, J. K., Hammond-Martel, I., Dar, H. H., Therrien, M., & Affar, E. B. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.03.002 · Cited by 195 · see citing works
Self-citationCancer-associated ASXL1 mutations may act as gain-of-function mutations of the ASXL1–BAP1 complex
Balasubramani, A., Larjo, A., Bassein, J. A., Chang, X., Hastie, R., Togher, S., Lähdesmäki, H. J., & Rao, A. (2015) · Nature Communications · doi:10.1038/ncomms8307 · Cited by 194 · see citing works
Enhancer selectivity in space and time: from enhancer–promoter interactions to promoter activation
Yang, J. H., & Hansen, A. S. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00710-6 · Cited by 191 · see citing works
Resetting the epigenetic balance of Polycomb and COMPASS function at enhancers for cancer therapy
Wang, L., Zhao, Z., Ozark, P. A., Fantini, D., Marshall, S. A., Rendleman, E. J., Cozzolino, K., Louis, N., He, X., Morgan, M. A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0034-6 · Cited by 184 · see citing works
Roles and mechanisms of BAP1 deubiquitinase in tumor suppression
Masclef, L., Ahmed, O., Estavoyer, B., Larrivée, B., Labrecque, N., Nijnik, A., & Affar, E. B. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-020-00709-4 · Cited by 184 · see citing works
Self-citationFOXK1 and FOXK2 regulate aerobic glycolysis
Sukonina, V., Ma, H., Zhang, W., Bartesaghi, S., Subhash, S., Heglind, M., Foyn, H., Betz, M. J., Nilsson, D., Lidell, M. E., et al. (2019) · Nature · doi:10.1038/s41586-019-0900-5 · Cited by 181 · see citing works
Transformation of normal human cells in the absence of telomerase activation
Seger, Y. R., Garcı́a-Cao, M., Piccinin, S., Cunsolo, C. L., Doglioni, C., Blasco, M. A., Hannon, G. J., & Maestro, R. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00183-6 · Cited by 159 · see citing works
Polycomb group-mediated histone H2A monoubiquitination in epigenome regulation and nuclear processes
Barbour, H., Daou, S., Hendzel, M. J., & Affar, E. B. (2020) · Nature Communications · doi:10.1038/s41467-020-19722-9 · Cited by 155 · see citing works
Self-citationFoxk proteins repress the initiation of starvation-induced atrophy and autophagy programs
Bowman, C. J., Ayer, D. E., & Dynlacht, B. D. (2014) · Nature Cell Biology · doi:10.1038/ncb3062 · Cited by 153 · see citing works
mTORC1 Promotes Metabolic Reprogramming by the Suppression of GSK3-dependent Foxk1 Phosphorylation
He, L., Gomes, A. P., Wang, X., Yoon, S. O., Lee, G., Nagiec, M. J., Cho, S., Chavez, A., Islam, T., Yu, Y., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.04.024 · Cited by 145 · see citing works
Daou, S., Hammond-Martel, I., Mashtalir, N., Barbour, H., Gagnon, J. K., Iannantuono, N., Nkwe, N. S., Motorina, A., Pak, H., Yu, H., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.661553 · Cited by 136 · see citing works
Self-citationLoss of expression of BAP1 predicts longer survival in mesothelioma
Farzin, M., Toon, C. W., Clarkson, A., Sioson, L., Watson, N., Andrici, J., & Gill, A. J. (2015) · Pathology · doi:10.1097/pat.0000000000000250 · Cited by 134 · see citing works
Mallette, F. A., & Richard, S. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.09.033 · Cited by 119 · see citing works
FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism
Sakaguchi, M., Cai, W., Wang, C., Cederquist, C., Damasio, M. P. S., Homan, E. P., Batista, T. M., Ramirez, A. K., Gupta, M. K., Steger, M., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09418-0 · Cited by 111 · see citing works
Shan, L., Zhou, X., Liu, X., Wang, Y., Su, D., Hou, Y., Yu, N., Yang, C., Liu, B., Gao, J., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.09.010 · Cited by 99 · see citing works
Daou, S., Mashtalir, N., Hammond-Martel, I., Pak, H., Yu, H., Sui, G., Vogel, J. L., Kristie, T. M., & Affar, E. B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013822108 · Cited by 98 · see citing works
Self-citationPeng, Y., Zhang, P., Huang, X., Yan, Q., Wu, M., Xie, R., Yao, W., Zhang, M., Nan, Q.-Z., Zhao, J., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.225 · Cited by 87 · see citing works
Hawke, T. J., Jiang, N., & Garry, D. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209200200 · Cited by 82 · see citing works
Epigenetic targeted therapy of stabilized BAP1 in ASXL1 gain-of-function mutated leukemia
Wang, L., Birch, N. W., Zhao, Z., Nestler, C. M., Kazmer, A., Shilati, A., Blake, A., Ozark, P. A., Rendleman, E. J., Zha, D., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00199-4 · Cited by 82 · see citing works
Okino, Y., Machida, Y., Frankland‐Searby, S., & Machida, Y. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.609834 · Cited by 81 · see citing works
O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis
Taparra, K., Wang, H., Malek, R., Lafargue, A., Barbhuiya, M. A., Wang, X., Simons, B. W., Ballew, M., Nugent, K., Groves, J., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci94844 · Cited by 80 · see citing works
Cell Cycle-dependent Regulation of the Forkhead Transcription Factor FOXK2 by CDK·Cyclin Complexes
Marais, A., Ji, Z., Child, E. S., Krause, E., Mann, D. J., & Sharrocks, A. D. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.154005 · Cited by 77 · see citing works
Monoubiquitination of ASXLs controls the deubiquitinase activity of the tumor suppressor BAP1
Daou, S., Barbour, H., Ahmed, O., Masclef, L., Baril, C., Nkwe, N. S., Tchelougou, D., Uriarte, M., Bonneil, É., Ceccarelli, D. F. J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06854-2 · Cited by 72 · see citing works
Self-citationTsai, K., Huang, C.-Y., Chang, C., Sun, Y., Chuang, W., & Hsiao, C. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600478200 · Cited by 71 · see citing works
Liu, Y., Ao, X., Jia, Z., Bai, X., Xu, Z., Hu, G., Jiang, X., Chen, M., & Wu, H. (2015) · Scientific Reports · doi:10.1038/srep08796 · Cited by 63 · see citing works
FOXK1 interaction with FHL2 promotes proliferation, invasion and metastasis in colorectal cancer
Wu, M., Wang, J., Tang, W., Zhan, X., Li, Y., Peng, Y., Huang, X., Bai, Y., Zhao, J., Li, A., et al. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.68 · Cited by 61 · see citing works
FOXA1 O-GlcNAcylation–mediated transcriptional switch governs metastasis capacity in breast cancer
Liu, Y., Yu, K., Kong, X., Zhang, K., Wang, L., Zhang, N., Chen, Q., Niu, M., Li, W., Zhong, X., et al. (2023) · Science Advances · doi:10.1126/sciadv.adg7112 · Cited by 61 · see citing works
Coexpression of FOXK1 and vimentin promotes EMT, migration, and invasion in gastric cancer cells
Zhang, H., Wu, X., Xiao, Y., Wu, L., Peng, Y., Tang, W., Liu, G., Sun, Y., Wang, J., Zhu, H., et al. (2018) · Journal of Molecular Medicine · doi:10.1007/s00109-018-1720-z · Cited by 54 · see citing works
Yang, L., Chen, S., Zhao, Q., Pan, C., Peng, L., Yu, H., Li, L., Ruan, J., Xia, J., Yang, H., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110302 · Cited by 50 · see citing works
Foxk1 recruits the Sds3 complex and represses gene expression in myogenic progenitors
Shi, X., Seldin, D. C., & Garry, D. J. (2012) · Biochemical Journal · doi:10.1042/bj20120563 · Cited by 44 · see citing works
Chen, S., Jiang, S., Hu, F., Xu, Y., Wang, T., & Mei, Q. (2017) · Oncology Reports · doi:10.3892/or.2017.5461 · Cited by 43 · see citing works
Zhang, F., Ma, X., Li, H., Zhang, Y., Li, X., Chen, L., Guo, G., Gao, Y., Gu, L., Xie, Y., et al. (2018) · International Journal of Cancer · doi:10.1002/ijc.31278 · Cited by 42 · see citing works
Yao, W., Peng, Y., Wu, M., Zhang, W., Zhang, M., Xie, R., Zhang, P., Bai, Y., Zhao, J., Li, A., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9457 · Cited by 40 · see citing works
FOXK1 plays an oncogenic role in the development of esophageal cancer
Chen, D., Wang, K., Li, X., Jiang, M., Ni, L., Xu, B., Chu, Y., Wang, W., Wang, H., Kang, H., et al. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.10.080 · Cited by 38 · see citing works
Oncogenic transformation of human cells: shortcomings of rodent model systems
Akagi, T. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.09.001 · Cited by 37 · see citing works
Hakiri, S., Osada, H., Ishiguro, F., Murakami, H., Murakami‐Tonami, Y., Yokoi, K., & Sekido, Y. (2015) · Cancer Science · doi:10.1111/cas.12698 · Cited by 33 · see citing works
Cao, H., Chu, X., Wang, Z., Guo, C., Shao, S., Xiao, J. Y., Zheng, J., & Zhang, D. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.04.068 · Cited by 33 · see citing works
Li, L., Gong, M., Zhao, Y., Zhao, X., & Li, Q. (2017) · Oncotarget · doi:10.18632/oncotarget.19713 · Cited by 31 · see citing works
Growing and dividing: how O-GlcNAcylation leads the way
Saunders, H. I., Dias, W. B., & Slawson, C. M. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105330 · Cited by 31 · see citing works
Wang, B., Zhang, X., Wang, W., Zhu, Z., Tang, F., Wang, D., Liu, X., Zhuang, H., & Xiao-ling, Y. A. N. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s157126 · Cited by 28 · see citing works
Downregulation of FOXK2 is associated with poor prognosis in patients with gastric cancer
Liu, X., Wei, X., Niu, W., Wang, D., Wang, B., & Zhuang, H. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9466 · Cited by 22 · see citing works
Transcriptome analysis and tumor suppressor requirements of STAT5‐induced senescence
Mallette, F. A., Moiseeva, O. V., Calabrese, V., Mao, B., Gaumont‐Leclerc, M., & Ferbeyre, G. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05192.x · Cited by 21 · see citing works
FOXK1 Participates in DNA Damage Response by Controlling 53BP1 Function
Tang, M., Feng, X., Pei, G., Srivastava, M., Wang, C., Chen, Z., Li, S., Zhang, H., Zhao, Z., Li, X., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108018 · Cited by 20 · see citing works
Mason, D. X., Keppler, D., Zhang, J., Jackson, T. J., Seger, Y. R., Matsui, S., Abreo, F., Cowell, J. K., Hannon, G. J., Lowe, S. W., et al. (2006) · Carcinogenesis · doi:10.1093/carcin/bgi264 · Cited by 18 · see citing works
Regulation and roles of FOXK2 in cancer
Kang, Y., Zhang, K., Sun, L., & Zhang, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.967625 · Cited by 17 · see citing works
Foxk1 regulates cancer progression
Garry, D. J., Maeng, G., & Garry, M. G. (2020) · Annals of Translational Medicine · doi:10.21037/atm-2020-94 · Cited by 9 · see citing works
Flagged first, then by citations
2 of the 101 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Opportunities for Therapeutic Modulation of O-GlcNAc
Cheng, S. S., Mody, A. C., & Woo, C. M. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.4c00417 · Cited by 61 · see citing works
Li, M. (2026) · Scientific Reports · doi:10.1038/s41598-025-32938-3 · Cited by 4 · see citing works
Pandey, A. K., Badruddeen, B., Akhtar, J., Khan, M. I., Ahmad, M., & Islam, A. (2026) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2026.113211 · Cited by 4 · see citing works
Palmer, M., Leo, A., Atyeo, N., Tomacari, C., Nguyen, X., & Papp, B. (2024) · Journal of Virology · doi:10.1128/jvi.00886-24 · Cited by 2 · see citing works
Wang, D., Yang, W., & Li, K. (2026) · MEDS Clinical Medicine · doi:10.23977/medsc.2026.070105
FOXK1: a multifaceted regulator in metabolic reprogramming and disease progression
He, T., Ma, G., & Yuan, G. (2026) · Biology Direct · doi:10.1186/s13062-026-00862-9
Tumor suppressor BAP1 emerges as a key regulator of metabolism and cell death in tumors
Fan, K., Yao, J., Wu, S., & Zhang, Y. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1868659
Shu, C., Chen, X., Fei, J., Wang, J., Yang, X., Zhou, D., & Li, S. (2026) · Current Genomics · doi:10.1016/j.curgen.2026.07.003
- Authors
- Masclef, L., Ahmed, O., Iannantuono, N., Gagnon, J., Gushul-Leclaire, M., Boulay, K., Estavoyer, B., Echbicheb, M., Poy, M., Ali Boubacar, K., Boubekeur, A., Menggad, S., Schcolnik-Cabrera, A., Balsalobre, A., Bonneil, E., Thibault, P., Hulea, L., Tanaka, Y., Antoine-Mallette, F., Drouin, J., & Affar, E. B.
- Affiliations
- Hôpital Maisonneuve-Rosemont (CA)
- Institute for Research in Immunology and Cancer (CA)
- Montreal Clinical Research Institute (CA)
- Corresponding author
- Affar, El Bachir
- ORCID
- Masclef, Louis
- Ahmed, Oumaima
- Iannantuono, Nicholas
- Gagnon, Jessica
- Gushul-Leclaire, Mila
- Boulay, Karine
- Echbicheb, Mohamed
- Poy, Marty
- Ali Boubacar, Kalidou
- Boubekeur, Amina
- Menggad, Saad
- Schcolnik-Cabrera, Alejandro
- Bonneil, Eric
- Thibault, Pierre
- Hulea, Laura
- Tanaka, Yoshiaki
- Antoine-Mallette, Frédérick
- Drouin, Jacques
- Affar, El Bachir
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2024-03-02
- Volume
- 16
- Issue
- 1
- Pages
- 5959-5959
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC12219458
- OpenAlex
- W4411874551
- Cited by
- 6
- References
- 101
- Citations by year
- 2026: 4 · 2024: 2
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Nature Communications (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Government of Canada (PJT-195721, MOP159539, PLL-192254)
- Alliance de recherche numérique du Canada
- National Institutes of Health
- University of California, San Francisco
- Canadian Institutes of Health Research (MOP159539, 192254_1, 195721_1)
- National Institute of General Medical Sciences (R01GM129325)
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- FOXK1, O-GlcNAcylation, BAP1, E2F pathway, E2F target genes, chromatin regulation, transcriptional repression, carcinogenesis, cell proliferation, tumor growth
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.
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