{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:18:09Z","timestamp":1788787089122,"version":"build-2803163510"},"reference-count":82,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of University and Research-MUR","award":["PE00000019"],"award-info":[{"award-number":["PE00000019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mucinous epithelial ovarian cancer (mEOC) is a rare subtype of epithelial ovarian cancer, characterized by poor responses to standard platinum-based chemotherapy. Polo-like kinase 1 (PLK1) is a key regulator of mitosis and cell cycle progression and its inhibition has been recently identified as a target in mEOC. In this study, we aimed to identify further therapeutic targets in mEOC using a CRISPR\/Cas9 library targeting 3015 genes, with and without treatment with onvansertib, a PLK1 inhibitor. We identified twelve genes associated with cell survival (ZC2HC1C, RPA2, KIN17, TUBG1, SMC2, CDC26, CDC42, HOXA9, TAF10, SENP1, MRPS31, and COPS2) and three genes (JUND, CARD9, and BCL2L2) in synthetic lethality with onvansertib treatment. We validated that SENP1 downregulation is important for the growth of mEOC cells through esiRNA interference and the use of a pharmacological inhibitor Momordin Ic. The downregulation of CARD9 and BCL2L2 combined with subtoxic doses of onvansertib interfered with mEOC cell growth. Interestingly, the combination of navitoclax, an inhibitor of BcL2 family members including BCL2L2, was synergistic in all four of the mEOC cell lines tested and substantially induced cell death through apoptosis. These data support the use of a combination of navitoclax and onvansertib as a new therapeutic strategy for mEOC.<\/jats:p>","DOI":"10.3390\/ijms26020472","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T07:00:47Z","timestamp":1736406047000},"page":"472","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma"],"prefix":"10.3390","volume":"26","author":[{"given":"Serena","family":"Petrella","sequence":"first","affiliation":[{"name":"Laboratory of Gynecological Preclinical Oncology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8980-6243","authenticated-orcid":false,"given":"Marika","family":"Colombo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9379-0301","authenticated-orcid":false,"given":"Mirko","family":"Marabese","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Grasselli","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopharmacology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Panfili","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopharmacology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Chiappa","sequence":"additional","affiliation":[{"name":"Laboratory of Gynecological Preclinical Oncology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4357-1228","authenticated-orcid":false,"given":"Valentina","family":"Sancisi","sequence":"additional","affiliation":[{"name":"Translational Research Laboratory, Azienda Unit\u00e0 Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Craparotta","sequence":"additional","affiliation":[{"name":"Computational Oncology Unit, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1627-0032","authenticated-orcid":false,"given":"Maria C.","family":"Barbera","sequence":"additional","affiliation":[{"name":"Computational Oncology Unit, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada A.","family":"Cassanmagnago","sequence":"additional","affiliation":[{"name":"Computational Oncology Unit, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4377-5079","authenticated-orcid":false,"given":"Marco","family":"Bolis","sequence":"additional","affiliation":[{"name":"Computational Oncology Unit, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-434X","authenticated-orcid":false,"given":"Giovanna","family":"Damia","sequence":"additional","affiliation":[{"name":"Laboratory of Gynecological Preclinical Oncology, Department of Experimental Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3322\/caac.21456","article-title":"Ovarian Cancer Statistics, 2018","volume":"68","author":"Torre","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3322\/caac.21559","article-title":"Epithelial Ovarian Cancer: Evolution of Management in the Era of Precision Medicine","volume":"69","author":"Lheureux","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"216057","DOI":"10.1016\/j.canlet.2023.216057","article-title":"Molecular Characteristics and Clinical Behaviour of Epithelial Ovarian Cancers","volume":"555","author":"Hollis","year":"2023","journal-title":"Cancer Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1080\/13543784.2019.1693999","article-title":"Mucinous Ovarian Cancer: Current Therapeutic Targets, Preclinical Progress, and Experimental Drugs","volume":"28","author":"Moioli","year":"2019","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1111\/IGC.0b013e3181dd0110","article-title":"Prognostic Relevance of Uncommon Ovarian Histology in Women with Stage III\/IV Epithelial Ovarian Cancer","volume":"20","author":"Mackay","year":"2010","journal-title":"Int. J. Gynecol. Cancer Off. J. Int. Gynecol. Cancer Soc."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chiappa, M., Petrella, S., Damia, G., Broggini, M., Guffanti, F., and Ricci, F. (2022). Present and Future Perspective on PLK1 Inhibition in Cancer Treatment. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.903016"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1258\/ebm.2011.011011","article-title":"Polo-like Kinases and DNA Damage Checkpoint: Beyond the Traditional Mitotic Functions","volume":"236","author":"Bahassi","year":"2011","journal-title":"Exp. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"249","DOI":"10.5483\/BMBRep.2014.47.5.061","article-title":"Polo-like Kinase-1 in DNA Damage Response","volume":"47","author":"Hyun","year":"2014","journal-title":"BMB Rep."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kalous, J., and Aleshkina, D. (2023). Multiple Roles of PLK1 in Mitosis and Meiosis. Cells, 12.","DOI":"10.3390\/cells12010187"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/j.celrep.2014.10.011","article-title":"The Oncogenic STP Axis Promotes Triple-Negative Breast Cancer via Degradation of the REST Tumor Suppressor","volume":"9","author":"Karlin","year":"2014","journal-title":"Cell Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.3748\/wjg.15.4177","article-title":"Overexpression of Polo-like Kinase1 Predicts a Poor Prognosis in Hepatocellular Carcinoma Patients","volume":"15","author":"He","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/j.1349-7006.2003.tb01411.x","article-title":"Polo-like Kinase 1 (PLK1) Is Overexpressed in Primary Colorectal Cancers","volume":"94","author":"Takahashi","year":"2003","journal-title":"Cancer Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1158\/1078-0432.CCR-14-2890","article-title":"Epithelial-Mesenchymal Transition Predicts Polo-like Kinase 1 Inhibitor-Mediated Apoptosis in Non-Small Cell Lung Cancer","volume":"22","author":"Ferrarotto","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1002\/pros.20050","article-title":"Polo-like Kinase 1 Is Overexpressed in Prostate Cancer and Linked to Higher Tumor Grades","volume":"60","author":"Weichert","year":"2004","journal-title":"Prostate"},{"key":"ref_15","first-page":"4172","article-title":"PLK1 Promotes Epithelial-Mesenchymal Transition and Metastasis of Gastric Carcinoma Cells","volume":"8","author":"Cai","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/sj.bjc.6601610","article-title":"Polo-like Kinase Isoform Expression Is a Prognostic Factor in Ovarian Carcinoma","volume":"90","author":"Weichert","year":"2004","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1034\/j.1600-0560.2002.290605.x","article-title":"Expression of Polo-like Kinase (PLK1) in Thin Melanomas: A Novel Marker of Metastatic Disease","volume":"29","author":"Kneisel","year":"2002","journal-title":"J. Cutan. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Iliaki, S., Beyaert, R., and Afonina, I.S. (2021). Polo-like Kinase 1 (PLK1) Signaling in Cancer and Beyond. Biochem. Pharmacol., 193.","DOI":"10.1016\/j.bcp.2021.114747"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"748","DOI":"10.4149\/neo_2015_089","article-title":"Downregulation of PLK1 by RNAi Attenuates the Tumorigenicity of Esophageal Squamous Cell Carcinoma Cells via Promoting Apoptosis and Inhibiting Angiogenesis","volume":"62","author":"Zhao","year":"2015","journal-title":"Neoplasma"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.3892\/ijo.2016.3352","article-title":"Cytotoxic Mechanism of PLK1 Inhibitor GSK461364 against Osteosarcoma: Mitotic Arrest, Apoptosis, Cellular Senescence, and Synergistic Effect with Paclitaxel","volume":"48","author":"Chou","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1158\/1078-0432.CCR-13-2506","article-title":"Phase I Study of Oral Rigosertib (ON 01910.Na), a Dual Inhibitor of the PI3K and Plk1 Pathways, in Adult Patients with Advanced Solid Malignancies","volume":"20","author":"Bowles","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5225","DOI":"10.1158\/0008-5472.CAN-11-0076","article-title":"Combined Gene Expression Profiling and RNAi Screening in Clear Cell Renal Cell Carcinoma Identify PLK1 and Other Therapeutic Kinase Targets","volume":"71","author":"Ding","year":"2011","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.tranon.2016.10.003","article-title":"PLK1, A Potential Target for Cancer Therapy","volume":"10","author":"Liu","year":"2017","journal-title":"Transl. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1158\/1535-7163.MCT-11-0765","article-title":"NMS-P937, an Orally Available, Specific Small-Molecule Polo-like Kinase 1 Inhibitor with Antitumor Activity in Solid and Hematologic Malignancies","volume":"11","author":"Valsasina","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.3892\/or.2017.5417","article-title":"Inhibiting PLK1 Induces Autophagy of Acute Myeloid Leukemia Cells via Mammalian Target of Rapamycin Pathway Dephosphorylation","volume":"37","author":"Tao","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1158\/1078-0432.CCR-23-3053","article-title":"Onvansertib in Combination with FOLFIRI and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Phase Ib Clinical Study","volume":"30","author":"Ahn","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dube, D. (2022). Polo-like Kinases: An Antimitotic Drug Target for Cancer Therapy. Protein Kinase Inhibitors, Elsevier.","DOI":"10.1016\/B978-0-323-91287-7.00002-8"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Affatato, R., Carrassa, L., Chil\u00e0, R., Lupi, M., Restelli, V., and Damia, G. (2020). Identification of PLK1 as a New Therapeutic Target in Mucinous Ovarian Carcinoma. Cancers, 12.","DOI":"10.3390\/cancers12030672"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17588359221095064","DOI":"10.1177\/17588359221095064","article-title":"Onvansertib and Paclitaxel Combined in Platinum-Resistant Ovarian Carcinomas","volume":"14","author":"Affatato","year":"2022","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/s41419-024-06894-1","article-title":"Onvansertib Treatment Overcomes Olaparib Resistance in High-Grade Ovarian Carcinomas","volume":"15","author":"Chiappa","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41392-023-01309-7","article-title":"CRISPR\/Cas9 Therapeutics: Progress and Prospects","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ymeth.2019.04.015","article-title":"Genome-Wide CRISPR-Cas9 Screening in Mammalian Cells","volume":"164\u2013165","author":"Yu","year":"2019","journal-title":"Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13046-022-02242-3","article-title":"Genome-Wide CRISPR\/Cas9 Library Screen Identifies PCMT1 as a Critical Driver of Ovarian Cancer Metastasis","volume":"41","author":"Zhang","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pfeifer, M., Brammeld, J.S., Price, S., Pilling, J., Bhavsar, D., Farcas, A., Bateson, J., Sundarrajan, A., Miragaia, R.J., and Guan, N. (2024). Genome-Wide CRISPR Screens Identify the YAP\/TEAD Axis as a Driver of Persister Cells in EGFR Mutant Lung Cancer. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06190-w"},{"key":"ref_35","unstructured":"(2024, November 11). Cas9_Activity_Assay_March2016.Pdf. Available online: https:\/\/portals.broadinstitute.org\/gpp\/public\/dir\/download?dirpath=protocols\/production&filename=Cas9_Activity_Assay_March2016.pdf."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Li, W., Xu, H., Xiao, T., Cong, L., Love, M.I., Zhang, F., Irizarry, R.A., Liu, J.S., Brown, M., and Liu, X.S. (2014). MAGeCK Enables Robust Identification of Essential Genes from Genome-Scale CRISPR\/Cas9 Knockout Screens. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0554-4"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/s41596-018-0113-7","article-title":"Integrative Analysis of Pooled CRISPR Genetic Screens Using MAGeCKFlute","volume":"14","author":"Wang","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Tomasova, K., Cumova, A., Seborova, K., Horak, J., Koucka, K., Vodickova, L., Vaclavikova, R., and Vodicka, P. (2020). DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome. Cancers, 12.","DOI":"10.3390\/cancers12071713"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e649","DOI":"10.1002\/ctm2.649","article-title":"Identification of Potent SENP1 Inhibitors That Inactivate SENP1\/JAK2\/STAT Signaling Pathway and Overcome Platinum Drug Resistance in Ovarian Cancer","volume":"11","author":"Zhang","year":"2021","journal-title":"Clin. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"104784","DOI":"10.1016\/j.tiv.2020.104784","article-title":"Natural Triterpenoid Saponin Momordin Ic Suppresses HepG2 Cell Invasion via COX-2 Inhibition and PPAR\u03b3 Activation","volume":"65","author":"Wang","year":"2020","journal-title":"Toxicol. In Vitro"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/s41419-019-1407-6","article-title":"BCL-2 Family Isoforms in Apoptosis and Cancer","volume":"10","author":"Warren","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.7150\/thno.64233","article-title":"Targeting the Anti-Apoptotic Bcl-2 Family Proteins: Machine Learning Virtual Screening and Biological Evaluation of New Small Molecules","volume":"12","author":"Valentini","year":"2022","journal-title":"Theranostics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/s41419-023-05963-1","article-title":"Bcl-2 Family Inhibitors Sensitize Human Cancer Models to Therapy","volume":"14","author":"Valentini","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1200\/JCO.2004.08.078","article-title":"Mucinous Epithelial Ovarian Cancer: A Separate Entity Requiring Specific Treatment","volume":"22","author":"Hess","year":"2004","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/s11864-021-00904-6","article-title":"Options for the Treatment of Mucinous Ovarian Carcinoma","volume":"22","author":"Craig","year":"2021","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nrm3819","article-title":"Polo-like Kinases: Structural Variations Lead to Multiple Functions","volume":"15","author":"Zitouni","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/onc.2017.379","article-title":"Plk1 Phosphorylation of Numb Leads to Impaired DNA Damage Response","volume":"37","author":"Shao","year":"2018","journal-title":"Oncogene"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7527","DOI":"10.2147\/OTT.S210575","article-title":"PLK1 Contributes to Autophagy by Regulating MYC Stabilization in Osteosarcoma Cells","volume":"12","author":"Mo","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.molcel.2018.11.010","article-title":"RIPK1 and Caspase-8 Ensure Chromosome Stability Independently of Their Role in Cell Death and Inflammation","volume":"73","author":"Liccardi","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.devcel.2016.04.023","article-title":"The Centrosome Undergoes Plk1-Independent Interphase Maturation during Inflammation and Mediates Cytokine Release","volume":"37","author":"Vertii","year":"2016","journal-title":"Dev. Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e10734","DOI":"10.7554\/eLife.10734","article-title":"Polo-like Kinase 1 Induces Epithelial-to-Mesenchymal Transition and Promotes Epithelial Cell Motility by Activating CRAF\/ERK Signaling","volume":"5","author":"Wu","year":"2016","journal-title":"eLife"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.jmb.2006.09.033","article-title":"A Tandem of SH3-like Domains Participates in RNA Binding in KIN17, a Human Protein Activated in Response to Genotoxics","volume":"364","author":"Schiltz","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1073\/pnas.0236176100","article-title":"Global Genome Repair Is Required to Activate KIN17, a UVC-Responsive Gene Involved in DNA Replication","volume":"100","author":"Masson","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3814","DOI":"10.1128\/MCB.25.9.3814-3830.2005","article-title":"The Human Stress-Activated Protein Kin17 Belongs to the Multiprotein DNA Replication Complex and Associates in Vivo with Mammalian Replication Origins","volume":"25","author":"Miccoli","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.1093\/nar\/gkg459","article-title":"Selective Interactions of Human Kin17 and RPA Proteins with Chromatin and the Nuclear Matrix in a DNA Damage- and Cell Cycle-Regulated Manner","volume":"31","author":"Miccoli","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s11010-020-03939-9","article-title":"Kin17 Facilitates Thyroid Cancer Cell Proliferation, Migration, and Invasion by Activating P38 MAPK Signaling Pathway","volume":"476","author":"Jiang","year":"2021","journal-title":"Mol. Cell. Biochem."},{"key":"ref_57","first-page":"607","article-title":"Kin17 Knockdown Suppresses the Migration and Invasion of Cervical Cancer Cells through NF-\u03baB-Snail Pathway","volume":"13","author":"Zhong","year":"2020","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/mc.23492","article-title":"KIN17 Promotes Cell Migration and Invasion Through Stimulating the TGF-\u03b2\/Smad2 Pathway in Hepatocellular Carcinoma","volume":"62","author":"Dai","year":"2023","journal-title":"Mol. Carcinog."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Zeng, T., Gao, H., Yu, P., He, H., Ouyang, X., Deng, L., and Zhang, Y. (2011). Up-Regulation of Kin17 Is Essential for Proliferation of Breast Cancer. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0025343"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1111\/1759-7714.14004","article-title":"KIN17 Promotes Tumor Metastasis by Activating EMT Signaling in Luminal-A Breast Cancer","volume":"12","author":"Huang","year":"2021","journal-title":"Thorac. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.21037\/tcr.2018.08.16","article-title":"Relationships of Kin17 Protein Expression with Clinical Features and Prognosis of Colorectal Cancer","volume":"7","author":"Ruan","year":"2018","journal-title":"Transl. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1097\/IGC.0000000000000928","article-title":"Elevated Expression of Kin17 in Cervical Cancer and Its Association with Cancer Cell Proliferation and Invasion","volume":"27","author":"Zhang","year":"2017","journal-title":"Int. J. Gynecol. Cancer Off. J. Int. Gynecol. Cancer Soc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"475","DOI":"10.3892\/ol.2021.12736","article-title":"Analysis of the Association between KIN17 Expression and the Clinical Features\/Prognosis of Epithelial Ovarian Cancer, and the Effects of KIN17 in SKOV3 Cells","volume":"21","author":"Chen","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.3892\/ol.2017.5707","article-title":"Upregulation of KIN17 Is Associated with Non-Small Cell Lung Cancer Invasiveness","volume":"13","author":"Zhang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Lin, M., Zhang, M., Yi, B., Chen, J., Wen, S., Chen, R., Chen, T., and Li, Z. (2024). Emerging Role of SENP1 in Tumorigenesis and Cancer Therapy. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1354323"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.gene.2016.09.040","article-title":"Inhibition of SUMO-Specific Protease 1 Induces Apoptosis of Astroglioma Cells by Regulating NF-\u03baB\/Akt Pathways","volume":"595","author":"Xia","year":"2016","journal-title":"Gene"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/jcb.29946","article-title":"SENP1 Participates in Irinotecan Resistance in Human Colon Cancer Cells","volume":"122","author":"Chen","year":"2021","journal-title":"J. Cell. Biochem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.canlet.2011.05.019","article-title":"SUMO-Specific Protease 1 Regulates the In Vitro and In Vivo Growth of Colon Cancer Cells with the Upregulated Expression of CDK Inhibitors","volume":"309","author":"Xu","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/S1470-2045(11)70058-4","article-title":"Mucinous Carcinomas of the Ovary and Colorectum: Different Organ, Same Dilemma","volume":"12","author":"Kelemen","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41419-021-03635-6","article-title":"SENP1-Mediated deSUMOylation of JAK2 Regulates Its Kinase Activity and Platinum Drug Resistance","volume":"12","author":"Li","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5200","DOI":"10.1002\/cam4.3122","article-title":"Identification of the Key Genes Associated with Chemotherapy Sensitivity in Ovarian Cancer Patients","volume":"9","author":"Zheng","year":"2020","journal-title":"Cancer Med."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wang, C., and Zhu, Y. (2022). CARD9 Contributes to Ovarian Cancer Cell Proliferation, Cycle Arrest, and Cisplatin Sensitivity. BMC Mol. Cell Biol., 23.","DOI":"10.1186\/s12860-022-00447-0"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/s41419-020-2417-0","article-title":"BCL-w: Apoptotic and Non-Apoptotic Role in Health and Disease","volume":"11","author":"Hartman","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1158\/0008-5472.CAN-07-5836","article-title":"ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor","volume":"68","author":"Tse","year":"2008","journal-title":"Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Pinto, B., Novais, P., Henriques, A.C., Carvalho-Tavares, J., Silva, P.M.A., and Bousbaa, H. (2022). Navitoclax Enhances the Therapeutic Effects of PLK1 Targeting on Lung Cancer Cells in 2D and 3D Culture Systems. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14061209"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1080\/15384101.2018.1559557","article-title":"Mitotic Slippage: An Old Tale with a New Twist","volume":"18","author":"Sinha","year":"2019","journal-title":"Cell Cycle Georget. Tex"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5517","DOI":"10.1172\/JCI122533","article-title":"PLK1 Stabilizes a MYC-Dependent Kinase Network in Aggressive B Cell Lymphomas","volume":"128","author":"Ren","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41408-023-00914-7","article-title":"PLK1 as a Cooperating Partner for BCL2-Mediated Antiapoptotic Program in Leukemia","volume":"13","author":"Shah","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrm3722","article-title":"Control of Apoptosis by the BCL-2 Protein Family: Implications for Physiology and Therapy","volume":"15","author":"Czabotar","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1093\/bioinformatics\/btw230","article-title":"Combenefit: An Interactive Platform for the Analysis and Visualization of Drug Combinations","volume":"32","author":"Fornari","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nmeth.3047","article-title":"Improved Vectors and Genome-Wide Libraries for CRISPR Screening","volume":"11","author":"Sanjana","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nchembio.2050","article-title":"Parallel shRNA and CRISPR-Cas9 Screens Enable Antiviral Drug Target Identification","volume":"12","author":"Deans","year":"2016","journal-title":"Nat. Chem. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/472\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:25:15Z","timestamp":1759919115000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/472"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,8]]},"references-count":82,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26020472"],"URL":"https:\/\/doi.org\/10.3390\/ijms26020472","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,8]]}}}