{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T21:07:41Z","timestamp":1773954461968,"version":"3.50.1"},"reference-count":166,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Second Century Fund (C2F), Chulalongkorn University","award":["C2F"],"award-info":[{"award-number":["C2F"]}]},{"name":"National Science, Research and Innovation Fund (NSRF), and King Mongkut\u2019s University of Technology North Bangkok","award":["KMUTNB-FF-67-B-24"],"award-info":[{"award-number":["KMUTNB-FF-67-B-24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Computation"],"abstract":"<jats:p>Cancer progression is primarily driven by disruptions in critical biological pathways, including ErbB signaling, p53-mediated apoptosis, and GSK3 signaling. However, experimental and clinical studies typically identify only limited disease-associated genes, challenging traditional pathway analysis methods that require larger gene sets. To overcome this limitation, reliably expanded gene sets are required to align with cancer-related pathways. Although various propagation methods are available, the key challenge is to select techniques that can effectively propagate signals from limited seed gene sets through protein interaction networks, thereby generating robust, expanded sets capable of revealing pathway disruptions in cancer. In this study, the number of seed genes was systematically varied to evaluate the alignment of pathways obtained from different propagation methods with known pathways using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations. Among the evaluated propagation methods, normalized Laplacian diffusion (NLD) demonstrated the strongest alignment with reference pathways, with an average area under the ROC curve (AUC) of 95.11% and an area under precision\u2013recall (AUPR) of 71.20%. Focusing specifically on well-established cancer pathways, we summarized the enriched pathways and discussed their biological relevance with limited gene input. Results from multiple runs were aggregated to identify genes consistently prioritized but absent from core pathway annotations, representing potential pathway extensions. Notable examples include RAC2 (ErbB pathway), FOXO3 and ESR1 (GSK3 signaling), and XIAP and BRD4 (p53 pathway), which were significantly associated with patient survival. Literature validation confirmed their biological relevance, underscoring their potential as prognostic markers and therapeutic targets. In summary, NLD-based diffusion proves effective for pathway discovery from limited input, extending beyond annotated members to reveal clinically relevant genes with therapeutic and biomarker potential.<\/jats:p>","DOI":"10.3390\/computation13110266","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T13:51:08Z","timestamp":1762782668000},"page":"266","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Normalized Laplacian Diffusion for Robust Cancer Pathway Extension and Critical Gene Identification from Limited Data"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6814-1518","authenticated-orcid":false,"given":"Panisa","family":"Janyasupab","sequence":"first","affiliation":[{"name":"Advance Virtual and Intelligent Computing (AVIC) Center, Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3439-6619","authenticated-orcid":false,"given":"Apichat","family":"Suratanee","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Faculty of Applied Science, King Mongkut\u2019s University of Technology North Bangkok, Bangkok 10800, Thailand"},{"name":"Intelligent and Nonlinear Dynamics Innovations Research Center, Science and Technology Research Institute, King Mongkut\u2019s University of Technology North Bangkok, Bangkok 10800, Thailand"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0416-8316","authenticated-orcid":false,"given":"Kitiporn","family":"Plaimas","sequence":"additional","affiliation":[{"name":"Advance Virtual and Intelligent Computing (AVIC) Center, Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Omics Sciences and Bioinformatics Center, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Centre of Excellence in Mathematics, Ministry of Higher Education, Science, Research, and Innovation, National University of Sciences, Bangkok 10400, Thailand"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.semcancer.2020.09.007","article-title":"Transcriptomics and solid tumors: The next frontier in precision cancer medicine","volume":"84","author":"Tsimberidou","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7288","DOI":"10.1038\/s41467-024-51859-9","article-title":"Unbiased discovery of cancer pathways and therapeutics using Pathway Ensemble Tool and Benchmark","volume":"15","author":"Wang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Borisov, N., Sorokin, M., Tkachev, V., Garazha, A., and Buzdin, A. (2020). Cancer gene expression profiles associated with clinical outcomes to chemotherapy treatments. BMC Med. Genom., 13.","DOI":"10.1186\/s12920-020-00759-0"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Khatri, P., Sirota, M., and Butte, A.J. (2012). Ten years of pathway analysis: Current approaches and outstanding challenges. PLoS Comput. Biol., 8.","DOI":"10.1371\/journal.pcbi.1002375"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/s41596-018-0103-9","article-title":"Pathway enrichment analysis and visualization of omics data using g: Profiler, GSEA, Cytoscape and EnrichmentMap","volume":"14","author":"Reimand","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"He, H., Shao, X., Li, Y., Gihu, R., Xie, H., Zhou, J., and Yan, H. (2021). Targeting signaling pathway networks in several malignant tumors: Progresses and challenges. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.675675"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4939-7219-7_1","article-title":"ErbB receptors and cancer","volume":"1652","author":"Wang","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1089\/cmb.2008.0081","article-title":"Analysis of gene sets based on the underlying regulatory network","volume":"16","author":"Shojaie","year":"2009","journal-title":"J. Comput. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Shojaie, A., and Michailidis, G. (2010). Network enrichment analysis in complex experiments. Stat. Appl. Genet. Mol. Biol., 9.","DOI":"10.2202\/1544-6115.1483"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Suratanee, A., and Plaimas, K. (2020). Heterogeneous network model to identify potential associations between plasmodium vivax and human proteins. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041310"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Suratanee, A., Buaboocha, T., and Plaimas, K. (2021). Prediction of human-plasmodium vivax protein associations from heterogeneous network structures based on machine-learning approach. Bioinform. Biol. Insights, 15.","DOI":"10.1177\/11779322211013350"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.csbj.2014.08.008","article-title":"The role of protein interaction networks in systems biomedicine","volume":"11","author":"Sevimoglu","year":"2014","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Liu, L., and Ruan, J. (2013, January 18\u201321). Network-based pathway enrichment analysis. Proceedings of the 2013 IEEE International Conference on Bioinformatics and Biomedicine, Shanghai, China.","DOI":"10.1109\/BIBM.2013.6732493"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Liu, L., Wei, J., and Ruan, J. (2017). Pathway enrichment analysis with networks. Genes, 8.","DOI":"10.3390\/genes8100246"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ran, J., Li, H., Fu, J., Liu, L., Xing, Y., Li, X., Shen, H., Chen, Y., Jiang, X., and Li, Y. (2013). Construction and analysis of the protein-protein interaction network related to essential hypertension. BMC Syst. Biol., 7.","DOI":"10.1186\/1752-0509-7-32"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Handen, A., and Ganapathiraju, M.K. (2015). LENS: Web-based lens for enrichment and network studies of human proteins. BMC Med. Genom., 4.","DOI":"10.1186\/1755-8794-8-S4-S2"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Chi, L., Ma, J., Wan, Y., Deng, Y., Wu, Y., Cen, X., Zhou, X., Zhao, X., Wang, Y., and Ji, Z. (2023). HGNNPIP: A Hybrid Graph Neural Network framework for Protein-protein Interaction Prediction. bioRxiv.","DOI":"10.1101\/2023.12.10.571021"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Janyasupab, P., Singhanat, K., Warnnissorn, M., Thuwajit, P., Suratanee, A., Plaimas, K., and Thuwajit, C. (2024). Identification of Tumor Budding-Associated Genes in Breast Cancer through Transcriptomic Profiling and Network Diffusion Analysis. Biomolecules, 14.","DOI":"10.3390\/biom14080896"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sagulkoo, P., Suratanee, A., and Plaimas, K. (2022). Immune-related protein interaction network in severe COVID-19 patients toward the identification of key proteins and drug repurposing. Biomolecules, 12.","DOI":"10.3390\/biom12050690"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wang, P.I., Hwang, S., Kincaid, R.P., Sullivan, C.S., Lee, I., and Marcotte, E.M. (2012). RIDDLE: Reflective diffusion and local extension reveal functional associations for unannotated gene sets via proximity in a gene network. Genome Biol., 13.","DOI":"10.1186\/gb-2012-13-12-r125"},{"key":"ref_21","first-page":"4","article-title":"Random walks on graphs","volume":"Volume 2","year":"1993","journal-title":"Combinatorics, Paul Erdos is Eighty"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Pan, J.-Y., Yang, H.-J., Faloutsos, C., and Duygulu, P. (2004, January 22\u201325). Automatic multimedia cross-modal correlation discovery. Proceedings of the tenth ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, Seattle, WA, USA.","DOI":"10.1145\/1014052.1014135"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.4137\/BBI.S35237","article-title":"DDA: A novel network-based scoring method to identify disease-disease associations","volume":"9","author":"Suratanee","year":"2015","journal-title":"Bioinform. Biol. Insights"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e1124","DOI":"10.7717\/peerj-cs.1124","article-title":"Heterogeneous network propagation with forward similarity integration to enhance drug\u2013target association prediction","volume":"8","author":"Tangmanussukum","year":"2022","journal-title":"PeerJ Comput. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/bioinformatics\/bty637","article-title":"Random walk with restart on multiplex and heterogeneous biological networks","volume":"35","author":"Valdeolivas","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Smola, A.J., and Kondor, R. (2003). Kernels and regularization on graphs. Learning Theory and Kernel Machines, Proceedings of the 16th Annual Conference on Learning Theory and 7th Kernel Workshop, COLT\/Kernel 2003, Washington, DC, USA, 24\u201327 August 2003, Springer.","DOI":"10.1007\/978-3-540-45167-9_12"},{"key":"ref_27","first-page":"1325","article-title":"Graph laplacians and their convergence on random neighborhood graphs","volume":"8","author":"Hein","year":"2007","journal-title":"J. Mach. Learn. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.3934\/mbe.2021147","article-title":"Network diffusion with centrality measures to identify disease-related genes","volume":"18","author":"Janyasupab","year":"2021","journal-title":"Math. Biosci. Eng."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Picart-Armada, S., Barrett, S.J., Will\u00e9, D.R., Perera-Lluna, A., Gutteridge, A., and Dessailly, B.H. (2019). Benchmarking network propagation methods for disease gene identification. PLoS Comput. Biol., 15.","DOI":"10.1371\/journal.pcbi.1007276"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sagulkoo, P., Suratanee, A., and Plaimas, K. (2022, January 21\u201323). Network-based methods with heterogeneous data to identify severe COVID immune-related genes. Proceedings of the 2022 26th International Computer Science and Engineering Conference (ICSEC), Sakon Nakhon, Thailand.","DOI":"10.1109\/ICSEC56337.2022.10049313"},{"key":"ref_31","unstructured":"Xie, M., Hwang, T., and Kuang, R. (June, January 29). Prioritizing disease genes by bi-random walk. Proceedings of the Pacific-Asia Conference on Knowledge Discovery and Data Mining, Kuala Lumpur, Malaysia."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nrg.2017.38","article-title":"Network propagation: A universal amplifier of genetic associations","volume":"18","author":"Cowen","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"iyad031","DOI":"10.1093\/genetics\/iyad031","article-title":"The gene ontology knowledgebase in 2023","volume":"224","author":"Aleksander","year":"2023","journal-title":"Genetics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"D587","DOI":"10.1093\/nar\/gkac963","article-title":"KEGG for taxonomy-based analysis of pathways and genomes","volume":"51","author":"Kanehisa","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"D258","DOI":"10.1093\/nar\/gkh036","article-title":"The Gene Ontology (GO) database and informatics resource","volume":"32","author":"Consortium","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_36","unstructured":"Pag\u00e8s, H., Carlson, M., Falcon, S., and Li, N. (2025, October 01). AnnotationDbi: Manipulation of SQLite-Based Annotations in Bioconductor, R Package Version 1.1; Bioconductor. Available online: https:\/\/bioconductor.org\/packages\/release\/bioc\/html\/AnnotationDbi.html."},{"key":"ref_37","unstructured":"Carlson, M., Falcon, S., Pages, H., and Li, N. (2025, October 01). org. Hs. eg. db: Genome Wide Annotation for Human, R Package Version 3.2; Bioconductor. Available online: https:\/\/bioconductor.org\/packages\/release\/data\/annotation\/html\/org.Hs.eg.db.html."},{"key":"ref_38","unstructured":"Carlson, M., Falcon, S., Pages, H., and Li, N. (2025, October 01). GO.db: A Set of Annotation Maps Describing the Entire Gene Ontology. Bioconductor, Available online: https:\/\/bioconductor.org\/packages\/release\/data\/annotation\/html\/GO.db.html."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Manjang, K., Tripathi, S., Yli-Harja, O., Dehmer, M., and Emmert-Streib, F. (2020). Graph-based exploitation of gene ontology using GOxploreR for scrutinizing biological significance. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-73326-3"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"D353","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: New perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_41","unstructured":"Tenenbaum, D., and Maintainer, B. (2025, October 01). KEGGREST: Client-Side REST Access to the Kyoto Encyclopedia of Genes and Genomes (KEGG), R Package Version 1.36.0; Bioconductor. Available online: https:\/\/bioconductor.org\/packages\/release\/bioc\/html\/KEGGREST.html."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chandraprasad, M.S., Dey, A., and Swamy, M.K. (2022). Introduction to cancer and treatment approaches. Paclitaxel, Elsevier.","DOI":"10.1016\/B978-0-323-90951-8.00010-2"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1016\/j.laa.2008.01.029","article-title":"On the spectrum of the normalized graph Laplacian","volume":"428","author":"Banerjee","year":"2008","journal-title":"Linear Algebra Its Appl."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110255","DOI":"10.1016\/j.knosys.2023.110255","article-title":"Network representation learning via improved random walk with restart","volume":"263","author":"Zhang","year":"2023","journal-title":"Knowl. Based Syst."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"W207","DOI":"10.1093\/nar\/gkad347","article-title":"g: Profiler\u2014Interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update)","volume":"51","author":"Kolberg","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"D672","DOI":"10.1093\/nar\/gkad1025","article-title":"The reactome pathway knowledgebase 2024","volume":"52","author":"Milacic","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D679","DOI":"10.1093\/nar\/gkad960","article-title":"WikiPathways 2024: Next generation pathway database","volume":"52","author":"Agrawal","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/ng.2764","article-title":"The cancer genome atlas pan-cancer analysis project","volume":"45","author":"Weinstein","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Voskas, D., Ling, L.S., and Woodgett, J.R. (2010). Does GSK-3 provide a shortcut for PI3K activation of Wnt signalling?. F1000 Biol. Rep., 2.","DOI":"10.3410\/B2-82"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"de Villenfagne, L., Sablon, A., and Demoulin, J.-B. (2024). PDGFRA K385 mutants in myxoid glioneuronal tumors promote receptor dimerization and oncogenic signaling. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-57859-5"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1038\/onc.2009.45","article-title":"PUMA, a potent killer with or without p53","volume":"27","author":"Yu","year":"2008","journal-title":"Oncogene"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.molcel.2010.11.029","article-title":"Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling in breast cancer","volume":"40","author":"Sosa","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"775","DOI":"10.18632\/oncotarget.1770","article-title":"Targeting Src-mediated Tyr216 phosphorylation and activation of GSK-3 in prostate cancer cells inhibit prostate cancer progression in vitro and in vivo","volume":"5","author":"Goc","year":"2014","journal-title":"Oncotarget"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.18632\/oncotarget.2037","article-title":"GSK-3 as potential target for therapeutic intervention in cancer","volume":"5","author":"McCubrey","year":"2014","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1042\/BJ20051493","article-title":"G\u03b1q binds to p110\u03b1\/p85\u03b1 phosphoinositide 3-kinase and displaces Ras","volume":"394","author":"Ballou","year":"2006","journal-title":"Biochem. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"52432","DOI":"10.1074\/jbc.M310982200","article-title":"Phospholipase C-independent activation of glycogen synthase kinase-3\u03b2 and C-terminal Src kinase by G\u03b1q","volume":"278","author":"Fan","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Alves, M., Borges, D.d.P., Kimberly, A., Martins Neto, F., Oliveira, A.C., Sousa, J.C.d., Nogueira, C.D., Carneiro, B.A., and Tavora, F. (2021). Glycogen Synthase Kinase-3 Beta Expression Correlates with Worse Overall Survival in Non-Small Cell Lung Cancer\u2014A Clinicopathological Series. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.621050"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1074\/jbc.M112.429936","article-title":"Dual regulation of glycogen synthase kinase 3 (GSK3) \u03b1\/\u03b2 by protein kinase C (PKC) \u03b1 and Akt promotes thrombin-mediated integrin \u03b1IIb\u03b23 activation and granule secretion in platelets","volume":"288","author":"Moore","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_61","first-page":"10","article-title":"The GSK3\u03b2 pathway in optic nerve regeneration","volume":"2","author":"Ahmed","year":"2020","journal-title":"Arch. Clin. Exp. Ophthalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1182\/bloodadvances.2019001393","article-title":"AKT signaling restrains tumor suppressive functions of FOXO transcription factors and GSK3 kinase in multiple myeloma","volume":"4","author":"Bloedjes","year":"2020","journal-title":"Blood Adv."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41419-020-2271-0","article-title":"Pten-mediated Gsk3\u03b2 modulates the na\u00efve pluripotency maintenance in embryonic stem cells","volume":"11","author":"Wang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1074\/jbc.M410090200","article-title":"The loss of glypican-3 induces alterations in Wnt signaling","volume":"280","author":"Song","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1210\/me.2007-0129","article-title":"Glycogen synthase kinase-3 protects estrogen receptor \u03b1 from proteasomal degradation and is required for full transcriptional activity of the receptor","volume":"21","author":"Grisouard","year":"2007","journal-title":"Mol. Endocrinol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"33006","DOI":"10.1074\/jbc.M506758200","article-title":"Glycogen synthase kinase-3 interacts with and phosphorylates estrogen receptor \u03b1 and is involved in the regulation of receptor activity","volume":"280","author":"Medunjanin","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1038\/onc.2011.35","article-title":"The pro-longevity gene FoxO3 is a direct target of the p53 tumor suppressor","volume":"30","author":"Renault","year":"2011","journal-title":"Oncogene"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1038\/s41467-019-09753-2","article-title":"Caspase-1 initiates apoptosis in the absence of gasdermin D","volume":"10","author":"Tsuchiya","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S1097-2765(00)80273-7","article-title":"Key roles for E2F1 in signaling p53-dependent apoptosis and in cell division within developing tumors","volume":"2","author":"Pan","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s43042-020-00089-x","article-title":"Exploring the multiple roles of guardian of the genome: P53","volume":"21","author":"Feroz","year":"2020","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1038\/sj.cdd.4401908","article-title":"Dissecting p53-dependent apoptosis","volume":"13","author":"Chipuk","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1038\/s41419-022-05505-1","article-title":"Regulation of programmed cell death by Brd4","volume":"13","author":"Hu","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1101\/gad.13.12.1501","article-title":"CDK inhibitors: Positive and negative regulators of G1-phase progression","volume":"13","author":"Sherr","year":"1999","journal-title":"Genes. Dev."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Nieva, P., Fern\u00e1ndez-Navarro, P., Vaquero-Lorenzo, C., Villa-Morales, M., Gra\u00f1a-Castro, O., Cobos-Fern\u00e1ndez, M.\u00c1., L\u00f3pez-Lorenzo, J.L., Llamas, P., Gonz\u00e1lez-Sanchez, L., and Sastre, I. (2018). RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4304-y"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1128\/MCB.19.1.12","article-title":"p53-mediated regulation of proliferating cell nuclear antigen expression in cells exposed to ionizing radiation","volume":"19","author":"Xu","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"939","DOI":"10.4161\/cc.3.7.972","article-title":"ATR, Claspin and the Rad9-Rad1-Hus1 complex regulate Chk1 and Cdc25A in the absence of DNA damage","volume":"3","author":"Lukas","year":"2004","journal-title":"Cell Cycle"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1038\/sj.onc.1209989","article-title":"p53 downregulates expression of the G1\/S cell cycle phosphatase Cdc25A","volume":"26","author":"Rother","year":"2007","journal-title":"Oncogene"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Duan, L., Perez, R.E., Calhoun, S., and Maki, C.G. (2022). RBL2\/DREAM-mediated repression of the Aurora kinase A\/B pathway determines therapy responsiveness and outcome in p53 WT NSCLC. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-05013-4"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1038\/s41418-022-00988-z","article-title":"Cell cycle regulation: p53-p21-RB signaling","volume":"29","author":"Engeland","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/s10495-024-01957-2","article-title":"ARTS and small-molecule ARTS mimetics upregulate p53 levels by promoting the degradation of XIAP","volume":"29","author":"Abbas","year":"2024","journal-title":"Apoptosis"},{"key":"ref_81","first-page":"306","article-title":"Simultaneous activation of p53 and inhibition of XIAP enhance the activation of apoptosis signaling pathways in AML","volume":"115","author":"Carter","year":"2010","journal-title":"Blood J. Am. Soc. Hematol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"31388","DOI":"10.1074\/jbc.M110.113878","article-title":"Direct binding of the EGF-like domain of neuregulin-1 to integrins (\u03b1v\u03b23 and \u03b16\u03b24) is involved in neuregulin-1\/ErbB signaling","volume":"285","author":"Ieguchi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1172\/JCI32278","article-title":"ErbB receptors: From oncogenes to targeted cancer therapies","volume":"117","author":"Zhang","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1093\/abbs\/gmt150","article-title":"Role of erbB3 receptors in cancer therapeutic resistance","volume":"46","author":"Lee","year":"2014","journal-title":"Acta Biochim Biophys Sin"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1158\/0008-5472.CAN-13-1625","article-title":"ERBB3-independent activation of the PI3K pathway in EGFR-mutant lung adenocarcinomas","volume":"75","author":"Song","year":"2015","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/s41467-019-08574-7","article-title":"Deregulated Gab2 phosphorylation mediates aberrant AKT and STAT3 signaling upon PIK3R1 loss in ovarian cancer","volume":"10","author":"Li","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"12165","DOI":"10.1073\/pnas.1206118109","article-title":"Neuregulin 1-ErbB4-PI3K signaling in schizophrenia and phosphoinositide 3-kinase-p110\u03b4 inhibition as a potential therapeutic strategy","volume":"109","author":"Law","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Shorning, B.Y., Dass, M.S., Smalley, M.J., and Pearson, H.B. (2020). The PI3K-AKT-mTOR pathway and prostate cancer: At the crossroads of AR, MAPK, and WNT signaling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124507"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Huang, R., Dai, Q., Yang, R., Duan, Y., Zhao, Q., Haybaeck, J., and Yang, Z. (2022). A review: PI3K\/AKT\/mTOR signaling pathway and its regulated eukaryotic translation initiation factors may be a potential therapeutic target in esophageal squamous cell carcinoma. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.817916"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5497","DOI":"10.1038\/onc.2008.245","article-title":"PI3K pathway alterations in cancer: Variations on a theme","volume":"27","author":"Yuan","year":"2008","journal-title":"Oncogene"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1177\/1756283X12448456","article-title":"Therapeutic targeting of the phosphatidylinositol 3-kinase signaling pathway: Novel targeted therapies and advances in the treatment of colorectal cancer","volume":"5","author":"Yu","year":"2012","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e76183","DOI":"10.7554\/eLife.76183","article-title":"FER-mediated phosphorylation and PIK3R2 recruitment on IRS4 promotes AKT activation and tumorigenesis in ovarian cancer cells","volume":"11","author":"Zhang","year":"2022","journal-title":"eLife"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Mohamadzade, Z., Soltani, B.M., Ghaemi, Z., and Hoseinpour, P. (2021). Cell specific tumor suppressor effect of Hsa-miR-1226-3p through downregulation of HER2, PIK3R2, and AKT1 genes. Int. J. Biochem. Cell Biol., 134.","DOI":"10.1016\/j.biocel.2021.105965"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"31","DOI":"10.21037\/sci.2016.07.02","article-title":"Will targeting PI3K\/Akt\/mTOR signaling work in hematopoietic malignancies?","volume":"3","author":"Gao","year":"2016","journal-title":"Stem Cell Investig."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"14413","DOI":"10.1002\/cam4.6068","article-title":"PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A","volume":"12","author":"Lin","year":"2023","journal-title":"Cancer Med."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Farhadi, P., and Park, T. (2025). The p130Cas-Crk\/CrkL Axis: A Therapeutic Target for Invasive Cancers Unveiled by Collaboration Among p130Cas, Crk, and CrkL. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26094017"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1177\/1947601912458687","article-title":"Roles for crk in cancer metastasis and invasion","volume":"3","author":"Tsuda","year":"2012","journal-title":"Genes Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.gendis.2014.10.002","article-title":"Mutant KRAS as a critical determinant of the therapeutic response of colorectal cancer","volume":"2","author":"Knickelbein","year":"2015","journal-title":"Genes Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3446","DOI":"10.1002\/cncr.28864","article-title":"The MAPK pathway across different malignancies: A new perspective","volume":"120","author":"Burotto","year":"2014","journal-title":"Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41698-024-00793-6","article-title":"Mechanisms of KRAS inhibitor resistance in KRAS-mutant colorectal cancer harboring Her2 amplification and aberrant KRAS localization","volume":"9","author":"Maruyama","year":"2025","journal-title":"NPJ Precis. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/onc.2009.312","article-title":"Shc is required for ErbB2-induced inhibition of apoptosis but is dispensable for cell proliferation and disruption of cell polarity","volume":"29","author":"Lucs","year":"2010","journal-title":"Oncogene"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/bcr327","article-title":"Intracellular signaling pathways of ErbB2\/HER-2 and family members","volume":"3","author":"Olayioye","year":"2001","journal-title":"Breast Cancer Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5178","DOI":"10.1128\/MCB.18.9.5178","article-title":"Tumor promoter arsenite activates extracellular signal-regulated kinase through a signaling pathway mediated by epidermal growth factor receptor and Shc","volume":"18","author":"Chen","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"23721","DOI":"10.1074\/jbc.M708360200","article-title":"Insulin-like growth factor-1 receptor and ErbB kinase inhibitor combinations block proliferation and induce apoptosis through cyclin D1 reduction and Bax activation","volume":"283","author":"Wilsbacher","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"114371","DOI":"10.18632\/oncotarget.22825","article-title":"Genomic alterations of ERBB receptors in cancer: Clinical implications","volume":"8","author":"Mishra","year":"2017","journal-title":"Oncotarget"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Chakravarty, D., Pedraza, A.M., Cotari, J., Liu, A.H., Punko, D., Kokroo, A., Huse, J.T., Altan-Bonnet, G., and Brennan, C.W. (2017). EGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-08940-9"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1215\/15228517-2009-003","article-title":"PDGFRA, PDGFRB, EGFR, and downstream signaling activation in malignant peripheral nerve sheath tumor","volume":"11","author":"Perrone","year":"2009","journal-title":"Neuro Oncol."},{"key":"ref_108","first-page":"8206","article-title":"FGFR1 and HER1 or HER2 co-amplification in breast cancer indicate poor prognosis","volume":"15","author":"Chen","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_109","first-page":"491","article-title":"Nuclear FGFR1 promotes pancreatic stellate cell-driven invasion through up-regulation of Neuregulin 1","volume":"42","author":"Coetzee","year":"2023","journal-title":"Oncogene"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.7150\/jca.40531","article-title":"FGF\/FGFR signaling pathway involved resistance in various cancer types","volume":"11","author":"Zhou","year":"2020","journal-title":"J. Cancer"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nature04177","article-title":"A quantitative protein interaction network for the ErbB receptors using protein microarrays","volume":"439","author":"Jones","year":"2006","journal-title":"Nature"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Schulze, W.X., Deng, L., and Mann, M. (2005). Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol. Syst. Biol., 1.","DOI":"10.1038\/msb4100012"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4736","DOI":"10.1073\/pnas.0810053106","article-title":"Noonan syndrome cardiac defects are caused by PTPN11 acting in endocardium to enhance endocardial-mesenchymal transformation","volume":"106","author":"Araki","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1126\/science.1141478","article-title":"MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling","volume":"316","author":"Engelman","year":"2007","journal-title":"Science"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"ra33","DOI":"10.1126\/scisignal.aac8460","article-title":"JAK2 inhibition sensitizes resistant EGFR-mutant lung adenocarcinoma to tyrosine kinase inhibitors","volume":"9","author":"Gao","year":"2016","journal-title":"Sci. Signal."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/sj.bjc.6604794","article-title":"Cross talk of signals between EGFR and IL-6R through JAK2\/STAT3 mediate epithelial\u2013mesenchymal transition in ovarian carcinomas","volume":"100","author":"Colomiere","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1161\/CIRCULATIONAHA.118.036099","article-title":"Endothelial cells regulate physiological cardiomyocyte growth via VEGFR2-mediated paracrine signaling","volume":"139","author":"Hemanthakumar","year":"2019","journal-title":"Circulation"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"4610","DOI":"10.1073\/pnas.0835895100","article-title":"Stabilization of \u03b2-catenin by a Wnt-independent mechanism regulates cardiomyocyte growth","volume":"100","author":"Haq","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"592","DOI":"10.4251\/wjgo.v8.i8.592","article-title":"Regulation of CTNNB1 signaling in gastric cancer and stem cells","volume":"8","author":"Tanabe","year":"2016","journal-title":"World. J. Gastrointest. Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"384","DOI":"10.4252\/wjsc.v8.i11.384","article-title":"Gene expression and pathway analysis of CTNNB1 in cancer and stem cells","volume":"8","author":"Tanabe","year":"2016","journal-title":"World J. Stem Cells"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cellsig.2018.03.004","article-title":"Dishevelled: A masterful conductor of complex Wnt signals","volume":"47","author":"Sharma","year":"2018","journal-title":"Cell. Signal."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Wu, G., Huang, H., Abreu, J.G., and He, X. (2009). Inhibition of GSK3 phosphorylation of \u03b2-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004926"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1083\/jcb.151.1.83","article-title":"Dishevelled-1 Regulates Microtubule StabilityA New Function Mediated by Glycogen Synthase Kinase-3\u03b2","volume":"151","author":"Krylova","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Ren, Q., Chen, J., and Liu, Y. (2021). LRP5 and LRP6 in Wnt signaling: Similarity and divergence. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.670960"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"MacDonald, B.T., and He, X. (2012). Frizzled and LRP5\/6 receptors for Wnt\/\u03b2-catenin signaling. Cold Spring Harb. Perspect. Biol., 4.","DOI":"10.1101\/cshperspect.a007880"},{"key":"ref_126","first-page":"2446","article-title":"Wnt3a-stimulated LRP6 phosphorylation is dependent upon arginine methylation of G3BP2.","volume":"125","author":"Bikkavilli","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1002\/jcp.25572","article-title":"Wnt3A Induces GSK-3\u03b2 Phosphorylation and \u03b2-Catenin Accumulation Through RhoA\/ROCK","volume":"232","author":"Kim","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"4421","DOI":"10.1242\/dev.02068","article-title":"The developmental biology of Dishevelled: An enigmatic protein governing cell fate and cell polarity","volume":"132","author":"Wallingford","year":"2005","journal-title":"Development"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1093\/emboj\/18.10.2823","article-title":"Interaction of Axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription","volume":"18","author":"Smalley","year":"1999","journal-title":"EMBO J."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.devcel.2015.01.031","article-title":"FOXKs promote Wnt\/\u03b2-catenin signaling by translocating DVL into the nucleus","volume":"32","author":"Wang","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1186\/s13287-024-03925-8","article-title":"DVL\/GSK3\/ISL1 pathway signaling: Unraveling the mechanism of SIRT3 in neurogenesis and AD therapy","volume":"15","author":"Dai","year":"2024","journal-title":"Stem Cell. Res. Ther."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.18632\/oncotarget.23149","article-title":"Recombinant frizzled1 protein attenuated cardiac hypertrophy after myocardial infarction via the canonical Wnt signaling pathway","volume":"9","author":"Fan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Martinez-Marin, D., Stroman, G.C., Fulton, C.J., and Pruitt, K. (2025). Frizzled receptors: Gatekeepers of Wnt signaling in development and disease. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1599355"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1002\/ijc.27746","article-title":"Frizzled homolog proteins, microRNAs and Wnt signaling in cancer","volume":"132","author":"Ueno","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.bbrc.2008.01.088","article-title":"Wnt7a interaction with Fzd5 and detection of signaling activation using a split eGFP","volume":"368","author":"Carmon","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"dev202545","DOI":"10.1242\/dev.202545","article-title":"Exploiting spatiotemporal regulation of FZD5 during neural patterning for efficient ventral midbrain specification","volume":"151","author":"Yang","year":"2024","journal-title":"Development"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"F35","DOI":"10.1152\/ajprenal.00136.2016","article-title":"Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis","volume":"311","author":"Beaton","year":"2016","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"5182","DOI":"10.4049\/jimmunol.1201819","article-title":"Wnt6 is expressed in granulomatous lesions of Mycobacterium tuberculosis\u2013infected mice and is involved in macrophage differentiation and proliferation","volume":"191","author":"Schaale","year":"2013","journal-title":"J. Immunol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.bone.2013.02.005","article-title":"PTEN regulation by the Akt\/GSK-3\u03b2 axis during RANKL signaling","volume":"55","author":"Jang","year":"2013","journal-title":"Bone"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Duda, P., Akula, S.M., Abrams, S.L., Steelman, L.S., Martelli, A.M., Cocco, L., Ratti, S., Candido, S., Libra, M., and Montalto, G. (2020). Targeting GSK3 and associated signaling pathways involved in cancer. Cells, 9.","DOI":"10.3390\/cells9051110"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Hoffmeister, L., Diekmann, M., Brand, K., and Huber, R. (2020). GSK3: A kinase balancing promotion and resolution of inflammation. Cells, 9.","DOI":"10.3390\/cells9040820"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.devcel.2009.06.016","article-title":"Wnt\/\u03b2-catenin signaling: Components, mechanisms, and diseases","volume":"17","author":"MacDonald","year":"2009","journal-title":"Dev. Cell"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.bbamcr.2008.02.016","article-title":"Insulin neuroprotection against oxidative stress is mediated by Akt and GSK-3\u03b2 signaling pathways and changes in protein expression","volume":"1783","author":"Duarte","year":"2008","journal-title":"Biochim. Et Biophys. Acta BBA-Mol. Cell Res."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Khan, M.Z., Zugaza, J.L., and Aleman, I.T. (2024). The signaling landscape of insulin-like growth factor 1. J. Biol. Chem., 301.","DOI":"10.1016\/j.jbc.2024.108047"},{"key":"ref_145","unstructured":"Sionov, R.V., Hayon, I.L., and Haupt, Y. (2001). The regulation of p53 growth suppression. Cell Cycle Checkp. Cancer Landes Biosci. Austin, 106\u2013125."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Nag, S., Qin, J., Srivenugopal, K.S., Wang, M., and Zhang, R. (2013). The MDM2-p53 pathway revisited. J. Biomed. Res., 27.","DOI":"10.7555\/JBR.27.20130030"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1177\/1947601912455199","article-title":"Dual roles of MDM2 in the regulation of p53: Ubiquitination dependent and ubiquitination independent mechanisms of MDM2 repression of p53 activity","volume":"3","author":"Shi","year":"2012","journal-title":"Genes Cancer"},{"key":"ref_148","first-page":"631","article-title":"The role of Cdc25A in the regulation of cell proliferation and apoptosis","volume":"12","author":"Shen","year":"2012","journal-title":"Anti-Cancer Agents Med. Chem. (Former. Curr. Med. Chem.-Anti-Cancer Agents)"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"5017","DOI":"10.1523\/JNEUROSCI.21-14-05017.2001","article-title":"Cyclin-dependent kinases and P53 pathways are activated independently and mediate Bax activation in neurons after DNA damage","volume":"21","author":"Morris","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_150","first-page":"a014407","article-title":"MYC and the control of apoptosis. Cold Spring Harb","volume":"4","author":"McMahon","year":"2014","journal-title":"Perspect. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"6236","DOI":"10.1093\/emboj\/cdf616","article-title":"MDM2\u2013HDAC1-mediated deacetylation of p53 is required for its degradation","volume":"21","author":"Ito","year":"2002","journal-title":"EMBO J."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.1523\/JNEUROSCI.6186-08.2009","article-title":"Histone deacetylase inhibitors prevent p53-dependent and p53-independent Bax-mediated neuronal apoptosis through two distinct mechanisms","volume":"29","author":"Uo","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41419-020-2399-y","article-title":"Life, death, and autophagy in cancer: NF-\u03baB turns up everywhere","volume":"11","author":"Verzella","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13045-021-01079-1","article-title":"Targeting MCL-1 in cancer: Current status and perspectives","volume":"14","author":"Wang","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1007\/s10495-011-0599-8","article-title":"Apoptosis induced by overall metabolic stress converges on the Bcl-2 family proteins Noxa and Mcl-1","volume":"16","author":"Wensveen","year":"2011","journal-title":"Apoptosis"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/cdd.2017.186","article-title":"BCL-2 family proteins: Changing partners in the dance towards death","volume":"25","author":"Kale","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1097\/01.jnen.0000263868.84188.3b","article-title":"Motor neuron disease in transgenic mice with an H46R mutant SOD1 gene","volume":"66","author":"Sasaki","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/sj.onc.1207220","article-title":"Distinct roles for p53, p27Kip1, and p21Cip1 during tumor development","volume":"23","author":"Kim","year":"2004","journal-title":"Oncogene"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"3943","DOI":"10.1038\/onc.2016.502","article-title":"Census and evaluation of p53 target genes","volume":"36","author":"Fischer","year":"2017","journal-title":"Oncogene"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"107669","DOI":"10.1016\/j.celrep.2020.107669","article-title":"Combined TP53 and RB1 loss promotes prostate cancer resistance to a spectrum of therapeutics and confers vulnerability to replication stress","volume":"31","author":"Nyquist","year":"2020","journal-title":"Cell Rep."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.drudis.2015.07.014","article-title":"A potential role of X-linked inhibitor of apoptosis protein in mitochondrial membrane permeabilization and its implication in cancer therapy","volume":"21","author":"Chaudhary","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1093\/rheumatology\/keac553","article-title":"A novel long non-coding RNA, lnc-RNU12, influences the T-cell cycle via c-JUN and CCNL2 in rheumatoid arthritis","volume":"62","author":"Mo","year":"2023","journal-title":"Rheumatology"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Imaizumi, Y., Furutachi, S., Watanabe, T., Miya, H., Kawaguchi, D., and Gotoh, Y. (2020). Role of the imprinted allele of the Cdkn1c gene in mouse neocortical development. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-58629-9"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1038\/sj.emboj.7600735","article-title":"Cell cycle-dependent nuclear retention of p53 by E2F1 requires phosphorylation of p53 at Ser315","volume":"24","author":"Fogal","year":"2005","journal-title":"EMBO J."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"3602","DOI":"10.1073\/pnas.91.9.3602","article-title":"p53 and E2F-1 cooperate to mediate apoptosis","volume":"91","author":"Wu","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/ncb1123","article-title":"Mitochondrial p53 activates Bak and causes disruption of a Bak\u2013Mcl1 complex","volume":"6","author":"Leu","year":"2004","journal-title":"Nat. Cell Biol."}],"container-title":["Computation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-3197\/13\/11\/266\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T14:19:08Z","timestamp":1762784348000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-3197\/13\/11\/266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":166,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["computation13110266"],"URL":"https:\/\/doi.org\/10.3390\/computation13110266","relation":{},"ISSN":["2079-3197"],"issn-type":[{"value":"2079-3197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]}}}