{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:55:44Z","timestamp":1790769344937,"version":"4.1.0"},"reference-count":129,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T00:00:00Z","timestamp":1649203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Post-translational modifications comprise series of enzymatically-driven chemical modifications, virtually involving the entire cell proteome, that affect the fate of a target protein and, in turn, cell activity. Different classes of modifications can be established ranging from phosphorylation, glycosylation, ubiquitination, acetylation, methylation, lipidation and their inverse reactions. Among these, SUMOylation and NEDDylation are ubiquitin-like multi-enzymatic processes that determine the bound of SUMOs and NEDD8 labels, respectively, on defined amino acidic residues of a specific protein and regulate protein function. As fate-determinants of several effectors and mediators, SUMOylation and NEDDylation play relevant roles in many aspects of tumor cell biology. Bone represents a preferential site of metastasis for solid tumors (e.g., breast and prostate cancers) and the primary site of primitive tumors (e.g., osteosarcoma, chondrosarcoma). Deregulation of SUMOylation and NEDDylation affects different aspects of neoplastic transformation and evolution such as epithelial-mesenchymal transition, adaptation to hypoxia, expression and action of tumor suppressors and oncogenic mediators, and drug resistance. Thereby, they represent potential therapeutic targets. This narrative review aims at describing the involvement and regulation of SUMOylation and NEDDylation in tumor biology, with a specific focus on primary and secondary bone tumors, and to summarize and highlight their potentiality in diagnostics and therapeutic strategies.<\/jats:p>","DOI":"10.3389\/fcell.2022.889002","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T06:23:33Z","timestamp":1649226213000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["SUMOylation and NEDDylation in Primary and Metastatic Cancers to Bone"],"prefix":"10.3389","volume":"10","author":[{"given":"Marta","family":"Gomarasca","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Lombardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Maroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1074\/jbc.M609001200","article-title":"FBXO11 Promotes the Neddylation of P53 and Inhibits its Transcriptional Activity","volume":"282","author":"Abida","year":"2007","journal-title":"J. Biol. Chem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/ng1752","article-title":"Genetic Regulators of Large-Scale Transcriptional Signatures in Cancer","volume":"38","author":"Adler","year":"2006","journal-title":"Nat. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"3954","DOI":"10.1038\/onc.2012.428","article-title":"NEDDylation Controls the Target Specificity of E2F1 and Apoptosis Induction","volume":"32","author":"Aoki","year":"2013","journal-title":"Oncogene"},{"key":"B4","doi-asserted-by":"publisher","first-page":"729550","DOI":"10.3389\/fonc.2021.729550","article-title":"A Different View for an Old Disease: NEDDylation and Other Ubiquitin-like Post-Translational Modifications in Chronic Lymphocytic Leukemia","volume":"11","author":"Arenas","year":"2021","journal-title":"Front. Oncol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"6272","DOI":"10.1038\/onc.2017.225","article-title":"Androgen Induces G3BP2 and SUMO-Mediated P53 Nuclear export in Prostate Cancer","volume":"36","author":"Ashikari","year":"2017","journal-title":"Oncogene"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.4161\/cc.5.14.3008","article-title":"A Novel Link between SUMO Modification and Cancer Metastasis","volume":"5","author":"Baek","year":"2006","journal-title":"Cell Cycle"},{"key":"B7","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1126\/science.1236188","article-title":"Nuclear PTEN Controls DNA Repair and Sensitivity to Genotoxic Stress","volume":"341","author":"Bassi","year":"2013","journal-title":"Science"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1073\/pnas.1416656112","article-title":"Src Phosphorylation Converts Mdm2 from a Ubiquitinating to a Neddylating E3 Ligase","volume":"112","author":"Batuello","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B9","doi-asserted-by":"publisher","first-page":"25859","DOI":"10.1074\/jbc.M110.134874","article-title":"SENP1 Induces Prostatic Intraepithelial Neoplasia through Multiple Mechanisms","volume":"285","author":"Bawa-Khalfe","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"17651","DOI":"10.18632\/oncotarget.13283","article-title":"SENP1 Regulates PTEN Stability to Dictate Prostate Cancer Development","volume":"8","author":"Bawa-Khalfe","year":"2017","journal-title":"Oncotarget"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1136\/gutjnl-2018-317856","article-title":"SUMO Pathway Inhibition Targets an Aggressive Pancreatic Cancer Subtype","volume":"69","author":"Biederst\u00e4dt","year":"2020","journal-title":"Gut"},{"key":"B12","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1158\/0008-5472.CAN-14-2824","article-title":"Regulation of Epithelial-Mesenchymal Transition through SUMOylation of Transcription Factors","volume":"75","author":"Bogachek","year":"2015","journal-title":"Cancer Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1091\/mbc.E21-01-0031","article-title":"SUMO Paralogue-specific Functions Revealed through Systematic Analysis of Human Knockout Cell Lines and Gene Expression Data","volume":"32","author":"Bouchard","year":"2021","journal-title":"MBoC"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1021\/acsmedchemlett.0c00353","article-title":"Synthesis and Evaluation of Ginkgolic Acid Derivatives as SUMOylation Inhibitors","volume":"11","author":"Brackett","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"B15","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1021\/acs.chemrev.6b00737","article-title":"Ubiquitin-like Protein Conjugation: Structures, Chemistry, and Mechanism","volume":"118","author":"Cappadocia","year":"2018","journal-title":"Chem. Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e0177639","DOI":"10.1371\/journal.pone.0177639","article-title":"Identification of the SUMO E3 Ligase PIAS1 as a Potential Survival Biomarker in Breast Cancer","volume":"12","author":"Chanda","year":"2017","journal-title":"PLoS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/jcb.29838","article-title":"The SUMO\u2010specific Protease SENP1 deSUMOylates P53 and Regulates its Activity","volume":"122","author":"Chauhan","year":"2021","journal-title":"J. Cel Biochem"},{"key":"B18","doi-asserted-by":"publisher","first-page":"5384","DOI":"10.1038\/ncomms6384","article-title":"CSN6 Drives Carcinogenesis by Positively Regulating Myc Stability","volume":"5","author":"Chen","year":"2014","journal-title":"Nat. Commun."},{"key":"B19","doi-asserted-by":"publisher","first-page":"5348","DOI":"10.1038\/sj.onc.1206851","article-title":"MDM2-ARF Complex Regulates P53 Sumoylation","volume":"22","author":"Chen","year":"2003","journal-title":"Oncogene"},{"key":"B20","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41392-020-0196-9","article-title":"Regulating Tumor Suppressor Genes: post-translational Modifications","volume":"5","author":"Chen","year":"2020","journal-title":"Sig Transduct Target. Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1586\/14737140.8.10.1689","article-title":"MYC in Breast Tumor Progression","volume":"8","author":"Chen","year":"2008","journal-title":"Expert Rev. Anticancer Ther."},{"key":"B22","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.gendis.2019.05.006","article-title":"Writing and Erasing MYC Ubiquitination and SUMOylation","volume":"6","author":"Chen","year":"2019","journal-title":"Genes Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"4560","DOI":"10.3390\/ijms16034560","article-title":"Roles of Ubiquitination and SUMOylation on Prostate Cancer: Mechanisms and Clinical Implications","volume":"16","author":"Chen","year":"2015","journal-title":"Ijms"},{"key":"B24","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/nature03918","article-title":"Crucial Role of P53-dependent Cellular Senescence in Suppression of Pten-Deficient Tumorigenesis","volume":"436","author":"Chen","year":"2005","journal-title":"Nature"},{"key":"B25","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1593\/neo.06445","article-title":"Role of Desumoylation in the Development of Prostate Cancer","volume":"8","author":"Cheng","year":"2006","journal-title":"Neoplasia"},{"key":"B26","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1016\/j.cell.2007.08.045","article-title":"SUMO-specific Protease 1 Is Essential for Stabilization of HIF1\u03b1 during Hypoxia","volume":"131","author":"Cheng","year":"2007","journal-title":"Cell"},{"key":"B27","doi-asserted-by":"publisher","first-page":"229","DOI":"10.18632\/oncoscience.27","article-title":"A Novel Role for the SUMO E3 Ligase PIAS1 in Cancer Metastasis","volume":"1","author":"Dadakhujaev","year":"2014","journal-title":"Oncoscience"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1054\/bjoc.2000.1522","article-title":"C-myc Amplification in Breast Cancer: a Meta-Analysis of its Occurrence and Prognostic Relevance","volume":"83","author":"Deming","year":"2000","journal-title":"Br. J. Cancer"},{"key":"B29","doi-asserted-by":"publisher","first-page":"14621","DOI":"10.1074\/jbc.M111.301523","article-title":"Overexpression of SKI Oncoprotein Leads to P53 Degradation through Regulation of MDM2 Protein Sumoylation","volume":"287","author":"Ding","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"4212","DOI":"10.1158\/0008-5472.CAN-20-1259","article-title":"SUMOylation of E2F1 Regulates Expression of EZH2","volume":"80","author":"Du","year":"2020","journal-title":"Cancer Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"667435","DOI":"10.3389\/fcell.2021.667435","article-title":"The Absence of PTEN in Breast Cancer Is a Driver of MLN4924 Resistance","volume":"9","author":"Du","year":"2021","journal-title":"Front. Cel Dev. Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s10549-018-4753-7","article-title":"Mutant P53 in Breast Cancer: Potential as a Therapeutic Target and Biomarker","volume":"170","author":"Duffy","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.3390\/cells9112359","article-title":"The Role of Sumoylation in the Response to Hypoxia: An Overview","volume":"9","author":"Filippopoulou","year":"2020","journal-title":"Cells"},{"key":"B34","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.chembiol.2009.01.009","article-title":"Ginkgolic Acid Inhibits Protein SUMOylation by Blocking Formation of the E1-SUMO Intermediate","volume":"16","author":"Fukuda","year":"2009","journal-title":"Chem. Biol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/s41591-020-01195-4","article-title":"Targeting Metastatic Cancer","volume":"27","author":"Ganesh","year":"2021","journal-title":"Nat. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.ejphar.2019.03.051","article-title":"SENP2 Suppresses NF-\u039ab Activation and Sensitizes Breast Cancer Cells to Doxorubicin","volume":"854","author":"Gao","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1038\/nrm3011","article-title":"The SUMO Pathway: Emerging Mechanisms that Shape Specificity, Conjugation and Recognition","volume":"11","author":"Gareau","year":"2010","journal-title":"Nat. Rev. Mol. Cel Biol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/978-3-030-38266-7_2","article-title":"Ubiquitin, SUMO, and Nedd8 as Therapeutic Targets in Cancer","volume":"1233","author":"G\u00e2tel","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1038\/nrm2293","article-title":"Concepts in Sumoylation: a Decade on","volume":"8","author":"Geiss-Friedlander","year":"2007","journal-title":"Nat. Rev. Mol. Cel Biol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1080\/15384101.2015.1040965","article-title":"c-Myc Is Targeted to the Proteasome for Degradation in a SUMOylation-dependent Manner, Regulated by PIAS1, SENP7 and RNF4","volume":"14","author":"Gonz\u00e1lez-Prieto","year":"2015","journal-title":"Cell Cycle"},{"key":"B41","doi-asserted-by":"publisher","first-page":"35103","DOI":"10.18632\/oncotarget.16626","article-title":"Ginkgolic Acids Inhibit Migration in Breast Cancer Cells by Inhibition of NEMO Sumoylation and NF-\u039ab Activity","volume":"8","author":"Hamdoun","year":"2017","journal-title":"Oncotarget"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.molcel.2005.03.012","article-title":"Sumo","volume":"18","author":"Hay","year":"2005","journal-title":"Mol. Cel"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1038\/nchembio.2463","article-title":"Probing the Roles of SUMOylation in Cancer Cell Biology by Using a Selective SAE Inhibitor","volume":"13","author":"He","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1038\/nsmb.2890","article-title":"Uncovering Global SUMOylation Signaling Networks in a Site-specific Manner","volume":"21","author":"Hendriks","year":"2014","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nsmb.3366","article-title":"Site-specific Mapping of the Human SUMO Proteome Reveals Co-modification with Phosphorylation","volume":"24","author":"Hendriks","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"2550","DOI":"10.1002\/ijc.33113","article-title":"UBC12 \u2010mediated SREBP \u20101 Neddylation Worsens Metastatic Tumor Prognosis","volume":"147","author":"Heo","year":"2020","journal-title":"Int. J. Cancer"},{"key":"B47","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1073\/pnas.0503698102","article-title":"PDSM, a Motif for Phosphorylation-dependent SUMO Modification","volume":"103","author":"Hietakangas","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2748","DOI":"10.1038\/emboj.2009.210","article-title":"SENP3 Is Responsible for HIF-1 Transactivation under Mild Oxidative Stress via P300 De-SUMOylation","volume":"28","author":"Huang","year":"2009","journal-title":"EMBO J."},{"key":"B49","doi-asserted-by":"publisher","first-page":"e37693","DOI":"10.1371\/journal.pone.0037693","article-title":"Triptolide Inhibits the Proliferation of Prostate Cancer Cells and Down-Regulates SUMO-specific Protease 1 Expression","volume":"7","author":"Huang","year":"2012","journal-title":"PLoS One"},{"key":"B50","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.yexcr.2018.07.005","article-title":"Talin Is a Substrate for SUMOylation in Migrating Cancer Cells","volume":"370","author":"Huang","year":"2018","journal-title":"Exp. Cel Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"00326","DOI":"10.1016\/j.semcdb.2021.12.010","article-title":"Stress - Regulation of SUMO Conjugation and of Other Ubiquitin\u2010Like Modifiers","author":"Ilic","year":"2022","journal-title":"Semin. Cel Develop. Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"3248","DOI":"10.1038\/s41388-018-0641-1","article-title":"Sumoylation of Flotillin-1 Promotes EMT in Metastatic Prostate Cancer by Suppressing Snail Degradation","volume":"38","author":"Jang","year":"2019","journal-title":"Oncogene"},{"key":"B53","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13046-020-01547-5","article-title":"A SUMOylation-dependent HIF-1\u03b1\/CLDN6 Negative Feedback Mitigates Hypoxia-Induced Breast Cancer Metastasis","volume":"39","author":"Jia","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1126\/science.1212728","article-title":"A SUMOylation-dependent Transcriptional Subprogram Is Required for Myc-Driven Tumorigenesis","volume":"335","author":"Kessler","year":"2012","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1038\/ncb1415","article-title":"Roles of Sumoylation of a Reptin Chromatin-Remodelling Complex in Cancer Metastasis","volume":"8","author":"Kim","year":"2006","journal-title":"Nat. Cel Biol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"531","DOI":"10.3390\/cancers13030531","article-title":"The Effect of Neddylation Blockade on Slug-dependent Cancer Cell Migration Is Regulated by P53 Mutation Status","volume":"13","author":"Kim","year":"2021","journal-title":"Cancers"},{"key":"B57","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1177\/1947601910379132","article-title":"MYC and Prostate Cancer","volume":"1","author":"Koh","year":"2010","journal-title":"Genes & Cancer"},{"key":"B58","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.tibs.2008.08.002","article-title":"HIF-1 Regulation: Not So Easy Come, Easy Go","volume":"33","author":"Koh","year":"2008","journal-title":"Trends Biochem. Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"3823","DOI":"10.3390\/cancers13153823","article-title":"SUMOylation Is Associated with Aggressive Behavior in Chondrosarcoma of Bone","volume":"13","author":"Kroonen","year":"2021","journal-title":"Cancers"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2501","DOI":"10.1021\/acs.jmedchem.0c01491","article-title":"Discovery of TAK-981, a First-In-Class Inhibitor of SUMO-Activating Enzyme for the Treatment of Cancer","volume":"64","author":"Langston","year":"2021","journal-title":"J. Med. Chem."},{"key":"B61","doi-asserted-by":"publisher","first-page":"5552","DOI":"10.1038\/s41388-018-0354-5","article-title":"The E3 Ligase C-CBL Inhibits Cancer Cell Migration by Neddylating the Proto-Oncogene C-Src","volume":"37","author":"Lee","year":"","journal-title":"Oncogene"},{"key":"B62","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/s41580-018-0015-0","article-title":"The Functions and Regulation of the PTEN Tumour Suppressor: New Modes and Prospects","volume":"19","author":"Lee","year":"","journal-title":"Nat. Rev. Mol. Cel Biol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1126\/science.275.5308.1943","article-title":"PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer","volume":"275","author":"Li","year":"1997","journal-title":"Science"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1016\/j.urolonc.2012.03.007","article-title":"Prognostic Impact of SUMO-specific Protease 1 (SENP1) in Prostate Cancer Patients Undergoing Radical Prostatectomy","volume":"31","author":"Li","year":"2013","journal-title":"Urol. Oncol. Semin. Original Invest."},{"key":"B65","doi-asserted-by":"publisher","first-page":"3780","DOI":"10.1038\/onc.2014.319","article-title":"NOTCH1 Activation in Breast Cancer Confers Sensitivity to Inhibition of SUMOylation","volume":"34","author":"Licciardello","year":"2015","journal-title":"Oncogene"},{"key":"B66","article-title":"Chondrosarcoma","volume-title":"Stat Pearls","author":"Limaiem","year":"2021"},{"key":"B67","doi-asserted-by":"publisher","first-page":"e89464","DOI":"10.1371\/journal.pone.0089464","article-title":"PIAS1 Regulates Breast Tumorigenesis through Selective Epigenetic Gene Silencing","volume":"9","author":"Liu","year":"2014","journal-title":"PLoS One"},{"key":"B68","doi-asserted-by":"publisher","first-page":"35477","DOI":"10.1074\/jbc.M504477200","article-title":"Pc2-mediated Sumoylation of Smad-Interacting Protein 1 Attenuates Transcriptional Repression of E-Cadherin","volume":"280","author":"Long","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B69","doi-asserted-by":"publisher","first-page":"jcs234120","DOI":"10.1242\/jcs.234120","article-title":"Inhibiting SUMO1-Mediated SUMOylation Induces Autophagy-Mediated Cancer Cell Death and Reduces Tumour Cell Invasion via RAC1","volume":"132","author":"Lorente","year":"2019","journal-title":"J. Cel Sci"},{"key":"B70","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/s0009-9120(01)00220-x","article-title":"Down Regulation of the Tumor Suppressor Gene Maspin in Breast Carcinoma Is Associated with a Higher Risk of Distant Metastasis","volume":"34","author":"Maass","year":"2001","journal-title":"Clin. Biochem."},{"key":"B71","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1158\/1078-0432.CCR-21-1565","article-title":"Relevance of pRB Loss in Human Malignancies","volume":"28","author":"Mandigo","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"B72","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1146\/annurev.cellbio.16.1.591","article-title":"SUMO-nonclassical Ubiquitin","volume":"16","author":"Melchior","year":"2000","journal-title":"Annu. Rev. Cel Dev. Biol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.1080\/15384101.2016.1182267","article-title":"SUMOylation of Rb Enhances its Binding with CDK2 and Phosphorylation at Early G1 Phase","volume":"15","author":"Meng","year":"2016","journal-title":"Cell Cycle"},{"key":"B74","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1016\/j.humpath.2010.02.007","article-title":"Expression Analysis of Ubc9, the Single Small Ubiquitin-like Modifier (SUMO) E2 Conjugating Enzyme, in normal and Malignant Tissues","volume":"41","author":"Moschos","year":"2010","journal-title":"Hum. Pathol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"659428","DOI":"10.3389\/fcell.2021.659428","article-title":"Cleavage of Syndecan-1 Promotes the Proliferation of the Basal-like Breast Cancer Cell Line BT-549 via Akt SUMOylation","volume":"9","author":"Nadanaka","year":"2021","journal-title":"Front. Cel Dev. Biol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/s41419-020-02838-7","article-title":"NEDDylation Negatively Regulates ERR\u03b2 Expression to Promote Breast Cancer Tumorigenesis and Progression","volume":"11","author":"Naik","year":"2020","journal-title":"Cell Death Dis"},{"key":"B77","doi-asserted-by":"publisher","first-page":"3004","DOI":"10.1038\/sj.onc.1202746","article-title":"MYC Oncogenes and Human Neoplastic Disease","volume":"18","author":"Nesbit","year":"1999","journal-title":"Oncogene"},{"key":"B78","first-page":"795","article-title":"Sumoylation of Transcription Factor ETV1 Modulates its Oncogenic Potential in Prostate Cancer","volume":"14","author":"Oh","year":"2021","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"18210","DOI":"10.1038\/s41598-020-75286-0","article-title":"Neddylation Blockade Induces HIF-1\u03b1 Driven Cancer Cell Migration via Upregulation of ZEB1","volume":"10","author":"Park","year":"2020","journal-title":"Sci. Rep."},{"key":"B80","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1042\/BJ20040198","article-title":"Getting into Position: the Catalytic Mechanisms of Protein Ubiquitylation","volume":"379","author":"Passmore","year":"2004","journal-title":"Biochem. J."},{"key":"B81","doi-asserted-by":"publisher","first-page":"5359","DOI":"10.3892\/etm.2018.6838","article-title":"SUMO-specific P-rotease 2 (SENP2) F-unctions as a T-umor S-uppressor in O-steosarcoma via SOX9 D-egradation","volume":"16","author":"Pei","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.4161\/cc.19847","article-title":"Posttranslational Control of Telomere Maintenance and the Telomere Damage Response","volume":"11","author":"Peuscher","year":"2012","journal-title":"Cell Cycle"},{"key":"B83","doi-asserted-by":"publisher","first-page":"14145","DOI":"10.1073\/pnas.97.26.14145","article-title":"Covalent Modification of the Androgen Receptor by Small Ubiquitin-like Modifier 1 (SUMO-1)","volume":"97","author":"Poukka","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B84","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1158\/2159-8290.CD-13-0136","article-title":"Contribution of P53 to Metastasis","volume":"4","author":"Powell","year":"2014","journal-title":"Cancer Discov."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1158\/0008-5472.CAN-16-2958","article-title":"The Role of PIAS SUMO E3-Ligases in Cancer","volume":"77","author":"Rabellino","year":"2017","journal-title":"Cancer Res."},{"key":"B86","doi-asserted-by":"publisher","first-page":"6963","DOI":"10.1074\/jbc.M110.188706","article-title":"Hypoxia-inducible Factor \u03b1 Subunit Stabilization by NEDD8 Conjugation Is Reactive Oxygen Species-dependent","volume":"286","author":"Ryu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B87","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1002\/iub.589","article-title":"Protein Monoubiquitination and Polyubiquitination Generate Structural Diversity to Control Distinct Biological Processes","volume":"64","author":"Sadowski","year":"2012","journal-title":"IUBMB Life"},{"key":"B88","doi-asserted-by":"publisher","first-page":"3803","DOI":"10.1042\/BCJ20200359","article-title":"SUMO E3 Ligase CBX4 Regulates hTERT-Mediated Transcription of CDH1 and Promotes Breast Cancer Cell Migration and Invasion","volume":"477","author":"Sanyal","year":"2020","journal-title":"Biochem. J."},{"key":"B89","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1038\/embor.2012.125","article-title":"Ubiquitin\u2010specific Protease\u2010like 1 (USPL1) Is a SUMO Isopeptidase with Essential, Non\u2010catalytic Functions","volume":"13","author":"Schulz","year":"2012","journal-title":"EMBO Rep."},{"key":"B90","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.molmed.2012.08.001","article-title":"Molecular Mechanisms Mediating Metastasis of Hypoxic Breast Cancer Cells","volume":"18","author":"Semenza","year":"2012","journal-title":"Trends Mol. Med."},{"key":"B91","doi-asserted-by":"publisher","first-page":"6429","DOI":"10.1038\/onc.2016.177","article-title":"SENP1-modulated Sumoylation Regulates Retinoblastoma Protein (RB) and Lamin A\/C Interaction and Stabilization","volume":"35","author":"Sharma","year":"2016","journal-title":"Oncogene"},{"key":"B92","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/embor.2012.3","article-title":"DeSUMOylating Isopeptidase: a Second Class of SUMO Protease","volume":"13","author":"Shin","year":"2012","journal-title":"EMBO Rep."},{"key":"B93","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/nature07884","article-title":"An Inhibitor of NEDD8-Activating Enzyme as a New Approach to Treat Cancer","volume":"458","author":"Soucy","year":"2009","journal-title":"Nature"},{"key":"B94","doi-asserted-by":"publisher","first-page":"3176","DOI":"10.4161\/cc.10.18.17436","article-title":"MDM2 Promotes SUMO-2\/3 Modification of P53 to Modulate Transcriptional Activity","volume":"10","author":"Stindt","year":"2011","journal-title":"Cell Cycle"},{"key":"B95","doi-asserted-by":"publisher","first-page":"10983","DOI":"10.1073\/pnas.1802932115","article-title":"SUMO Protease SENP1 deSUMOylates and Stabilizes C-Myc","volume":"115","author":"Sun","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B96","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.trecan.2019.11.004","article-title":"Mutant P53 on the Path to Metastasis","volume":"6","author":"Tang","year":"2020","journal-title":"Trends Cancer"},{"key":"B97","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.3390\/cancers13092059","article-title":"SENP Proteases as Potential Targets for Cancer Therapy","volume":"13","author":"Tokarz","year":"2021","journal-title":"Cancers"},{"key":"B98","doi-asserted-by":"publisher","first-page":"2660","DOI":"10.3390\/cells10102660","article-title":"The Many Potential Fates of Non-canonical Protein Substrates Subject to NEDDylation","volume":"10","author":"Vijayasimha","year":"2021","journal-title":"Cells"},{"key":"B99","doi-asserted-by":"publisher","first-page":"395","DOI":"10.7150\/ijbs.27256","article-title":"SENP1 Interacts with HIF1\u03b1 to Regulate Glycolysis of Prostatic Carcinoma Cells","volume":"15","author":"Wang","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.3892\/etm.2014.1644","article-title":"Inhibition of SENP5 Suppresses Cell Growth and Promotes Apoptosis in Osteosarcoma Cells","volume":"7","author":"Wang","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"B101","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1038\/onc.2012.250","article-title":"SUMO-specific Protease 1 Promotes Prostate Cancer Progression and Metastasis","volume":"32","author":"Wang","year":"2013","journal-title":"Oncogene"},{"key":"B102","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/974309","article-title":"Targeting the Neddylation Pathway to Suppress the Growth of Prostate Cancer Cells: Therapeutic Implication for the Men's Cancer","volume":"2014","author":"Wang","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"B103","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1002\/jcb.26342","article-title":"SENP1\/HIF\u20101\u03b1 Feedback Loop Modulates Hypoxia\u2010induced Cell Proliferation, Invasion, and EMT in Human Osteosarcoma Cells","volume":"119","author":"Wang","year":"2018","journal-title":"J. Cel. Biochem."},{"key":"B104","doi-asserted-by":"publisher","first-page":"603","DOI":"10.5732\/cjc.011.10226","article-title":"Epithelial-mesenchymal Transition in Breast Cancer Progression and Metastasis","volume":"30","author":"Wang","year":"2011","journal-title":"Chin. J. Cancer"},{"key":"B105","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1158\/0008-5472.CAN-11-2866","article-title":"Radiosensitization of Human Pancreatic Cancer Cells by MLN4924, an Investigational NEDD8-Activating Enzyme Inhibitor","volume":"72","author":"Wei","year":"2012","journal-title":"Cancer Res."},{"key":"B106","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1002\/ijc.10294","article-title":"Nuclear PTEN Expression and Clinicopathologic Features in a Population-Based Series of Primary Cutaneous Melanoma","volume":"99","author":"Whiteman","year":"2002","journal-title":"Int. J. Cancer"},{"key":"B107","doi-asserted-by":"publisher","first-page":"72","DOI":"10.3390\/ijms20010072","article-title":"MLN4924, a Protein Neddylation Inhibitor, Suppresses the Growth of Human Chondrosarcoma through Inhibiting Cell Proliferation and Inducing Endoplasmic Reticulum Stress-Related Apoptosis","volume":"20","author":"Wu","year":"2018","journal-title":"Ijms"},{"key":"B108","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1002\/1878-0261.12967","article-title":"SENP3 Loss Promotes M2 Macrophage Polarization and Breast Cancer Progression","volume":"16","author":"Xiao","year":"2021","journal-title":"Mol. Oncol."},{"key":"B109","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/s41422-021-00470-4","article-title":"Author Correction: Neddylation of PTEN Regulates its Nuclear Import and Promotes Tumor Development","volume":"31","author":"Xie","year":"","journal-title":"Cell Res"},{"key":"B110","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/s41422-020-00443-z","article-title":"Neddylation of PTEN Regulates its Nuclear Import and Promotes Tumor Development","volume":"31","author":"Xie","year":"","journal-title":"Cel Res"},{"key":"B111","doi-asserted-by":"publisher","first-page":"3733","DOI":"10.1038\/ncomms4733","article-title":"The Covalent Modifier Nedd8 Is Critical for the Activation of Smurf1 Ubiquitin Ligase in Tumorigenesis","volume":"5","author":"Xie","year":"2014","journal-title":"Nat. Commun."},{"key":"B112","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.cell.2004.06.016","article-title":"Mdm2-mediated NEDD8 Conjugation of P53 Inhibits its Transcriptional Activity","volume":"118","author":"Xirodimas","year":"2004","journal-title":"Cell"},{"key":"B113","doi-asserted-by":"publisher","first-page":"2040008","DOI":"10.1142\/S1793984420400085","article-title":"Emerging Role of Protein Post-Translational Modification in the Potential Clinical Application of Cancer","volume":"10","author":"Xue","year":"2020","journal-title":"Nano LIFE"},{"key":"B114","doi-asserted-by":"publisher","first-page":"e34079","DOI":"10.1371\/journal.pone.0034079","article-title":"The P21-dependent Radiosensitization of Human Breast Cancer Cells by MLN4924, an Investigational Inhibitor of NEDD8 Activating Enzyme","volume":"7","author":"Yang","year":"2012","journal-title":"PLoS One"},{"key":"B115","doi-asserted-by":"publisher","first-page":"5083","DOI":"10.1038\/sj.emboj.7601383","article-title":"An Extended Consensus Motif Enhances the Specificity of Substrate Modification by SUMO","volume":"25","author":"Yang","year":"2006","journal-title":"EMBO J."},{"key":"B116","doi-asserted-by":"publisher","first-page":"20528","DOI":"10.1073\/pnas.1905973116","article-title":"The FBXW2-MSX2-SOX2 axis Regulates Stem Cell Property and Drug Resistance of Cancer Cells","volume":"116","author":"Yin","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B117","doi-asserted-by":"publisher","first-page":"5700","DOI":"10.3390\/cancers13225700","article-title":"The Role of Protein SUMOylation in Human Hepatocellular Carcinoma: A Potential Target of New Drug Discovery and Development","volume":"13","author":"Yuan","year":"2021","journal-title":"Cancers"},{"key":"B118","first-page":"898","article-title":"ZNF451 Stabilizes TWIST2 through SUMOylation and Promotes Epithelial-Mesenchymal Transition","volume":"11","author":"Zeng","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"B119","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.3892\/ijo.2018.4448","article-title":"Silencing Ubc9 Expression Suppresses Osteosarcoma Tumorigenesis and Enhances Chemosensitivity to HSV-TK\/GCV by Regulating Connexin\ufffd43 SUMOylation","volume":"53","author":"Zhang","year":"2018","journal-title":"Int. J. Oncol."},{"key":"B120","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/s41418-018-0158-8","article-title":"SREBP1, Targeted by miR-18a-5p, Modulates Epithelial-Mesenchymal Transition in Breast Cancer via Forming a Co-repressor Complex with Snail and HDAC1\/2","volume":"26","author":"Zhang","year":"2019","journal-title":"Cell Death Differ"},{"key":"B121","doi-asserted-by":"publisher","first-page":"7741","DOI":"10.1007\/s13277-015-4406-y","article-title":"SENP1 Regulates Hepatocyte Growth Factor-Induced Migration and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma","volume":"37","author":"Zhang","year":"2016","journal-title":"Tumor Biol."},{"key":"B122","doi-asserted-by":"publisher","first-page":"45263","DOI":"10.18632\/oncotarget.9481","article-title":"MLN4924 Suppresses Neddylation and Induces Cell Cycle Arrest, Senescence, and Apoptosis in Human Osteosarcoma","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"B123","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.yexcr.2017.06.019","article-title":"Inhibition of Mcl-1 Enhances Pevonedistat-Triggered Apoptosis in Osteosarcoma Cells","volume":"358","author":"Zhang","year":"2017","journal-title":"Exp. Cel Res."},{"key":"B124","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s12938-021-00860-0","article-title":"Osteosarcoma: a Review of Current and Future Therapeutic Approaches","volume":"20","author":"Zhao","year":"2021","journal-title":"Biomed. Eng. Online"},{"key":"B125","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s12943-019-0979-1","article-title":"Neddylation: a Novel Modulator of the Tumor Microenvironment","volume":"18","author":"Zhou","year":"2019","journal-title":"Mol. Cancer"},{"key":"B126","doi-asserted-by":"publisher","first-page":"2624","DOI":"10.1038\/onc.2015.323","article-title":"Neddylation Controls Basal MKK7 Kinase Activity in Breast Cancer Cells","volume":"35","author":"Zhu","year":"2016","journal-title":"Oncogene"},{"key":"B127","doi-asserted-by":"publisher","first-page":"5754","DOI":"10.3390\/ijms22115754","article-title":"The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression","volume":"22","author":"Zou","year":"2021","journal-title":"Ijms"},{"key":"B128","doi-asserted-by":"publisher","first-page":"3884","DOI":"10.1111\/febs.15584","article-title":"Diverse and Pivotal Roles of Neddylation in Metabolism and Immunity","volume":"288","author":"Zou","year":"2021","journal-title":"FEBS J."},{"key":"B129","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.molcel.2012.12.002","article-title":"c-Cbl-Mediated Neddylation Antagonizes Ubiquitination and Degradation of the TGF-\u03b2 Type II Receptor","volume":"49","author":"Zuo","year":"2013","journal-title":"Mol. Cel"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.889002\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T06:23:39Z","timestamp":1649226219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.889002\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,6]]},"references-count":129,"alternative-id":["10.3389\/fcell.2022.889002"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2022.889002","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,6]]},"article-number":"889002"}}