{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T19:38:22Z","timestamp":1768073902165,"version":"3.49.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["GC16173472GARC"],"award-info":[{"award-number":["GC16173472GARC"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008431","name":"Consejer\u00eda de Educaci\u00f3n, Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["CSI018P23"],"award-info":[{"award-number":["CSI018P23"]}],"id":[{"id":"10.13039\/501100008431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PLEC2022-009217"],"award-info":[{"award-number":["PLEC2022-009217"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010434","name":"\u201cla Caixa\u201d Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010434","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:p>RHO family GTPases are key regulators of cancer-related processes such as cytoskeletal dynamics and cell migration, proliferation, and survival. Despite this, a comprehensive understanding of RHO signaling alterations across tumors is still lacking. In this study, we present a pan-cancer analysis of 484 genes encoding RHO GTPases, regulators, proximal effectors, distal downstream signaling elements, and components of their proximal interactomes using data from over 10,000 tumor samples and 33 tumor types present in The Cancer Genome Atlas (TCGA). In addition, we have utilized available data from genome-wide functional dependency screens performed in more than 1,000 gene-edited cancer cell lines. This study has uncovered positively selected mutations in both well-known and previously uncharacterized RHO pathway genes. Transcriptomic profiling reveals widespread and tumor-specific differential expression patterns, with some of them correlating with copy number changes. Interestingly, certain regulators exhibit consistent expression profiles across tumors opposite to those predicted from their canonical roles. Co-expression and gene set enrichment analyses highlight coordinated transcriptional programs involving some RHO GTPase pathway genes and their linkage to key cancer hallmarks, including extracellular matrix reorganization, cell motility, cell cycle progression, cell survival, and immune modulation. Functional screens further identify context-specific dependencies on several deregulated RHO GTPase pathway genes. Altogether, this study provides a comprehensive map of RHO GTPase pathway alterations in cancer and identifies new oncogenic drivers, expression-based signatures, and therapeutic vulnerabilities that could guide future mechanistic and translational research in this area.<\/jats:p>","DOI":"10.3389\/fbinf.2025.1708800","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:37:19Z","timestamp":1765953439000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Pan-cancer analyses identify oncogenic drivers, expression signatures, and therapeutic vulnerabilities in RHO GTPase pathway genes"],"prefix":"10.3389","volume":"5","author":[{"given":"Rub\u00e9n","family":"Fern\u00e1ndez","sequence":"first","affiliation":[]},{"given":"L. Francisco","family":"Lorenzo-Mart\u00edn","sequence":"additional","affiliation":[]},{"given":"V\u00edctor","family":"Quesada","sequence":"additional","affiliation":[]},{"given":"Xos\u00e9 R.","family":"Bustelo","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1073\/pnas.1608839114","article-title":"Activating mutations and translocations in the guanine exchange factor VAV1 in peripheral T-cell lymphomas","volume":"114","author":"Abate","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B2","doi-asserted-by":"publisher","first-page":"4788","DOI":"10.1093\/bioinformatics\/btz588","article-title":"OncodriveCLUSTL: a sequence-based clustering method to identify cancer drivers","volume":"35","author":"Arnedo-Pac","year":"2019","journal-title":"Bioinformatics"},{"key":"B3","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41556-019-0438-7","article-title":"Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms","volume":"22","author":"Bagci","year":"2020","journal-title":"Nat. Cell Biology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"861054","DOI":"10.1101\/861054","article-title":"Calling somatic SNVs and indels with Mutect2","author":"Benjamin","year":"2019","journal-title":"BioRxiv"},{"key":"B5","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1038\/nature11071","article-title":"Melanoma genome sequencing reveals frequent PREX2 mutations","volume":"485","author":"Berger","year":"2012","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e0188772","DOI":"10.1371\/journal.pone.0188772","article-title":"Comparative cell cycle transcriptomics reveals synchronization of developmental transcription factor networks in cancer cells","volume":"12","author":"Bostrom","year":"2017","journal-title":"PloS One"},{"key":"B7","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1042\/bst20170531","article-title":"RHO GTPases in cancer: known facts, open questions, and therapeutic challenges","volume":"46","author":"Bustelo","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"B8","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1002\/bies.20558","article-title":"GTP-binding proteins of the Rho\/Rac family: regulation, effectors and functions in vivo","volume":"29","author":"Bustelo","year":"2007","journal-title":"Bioessays"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.3390\/biology11101411","article-title":"CiberAMP: an R package to identify differential mRNA expression linked to somatic copy number variations in cancer datasets","volume":"11","author":"Caloto","year":"2022","journal-title":"Biol. (Basel)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive molecular portraits of human breast tumours","volume":"490","author":"Cancer Genome Atlas","year":"2012","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","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":"B12","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/nbt.3391","article-title":"Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity","volume":"34","author":"Chang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"10824","DOI":"10.1074\/jbc.m208310200","article-title":"Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma","volume":"278","author":"Ching","year":"2003","journal-title":"J. Biological Chemistry"},{"key":"B14","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1053\/j.gastro.2017.05.012","article-title":"Sporadic early-onset diffuse gastric cancers have high frequency of somatic CDH1 alterations, but low frequency of somatic RHOA mutations compared with late-onset cancers","volume":"153","author":"Cho","year":"2017","journal-title":"Gastroenterol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"ra71","DOI":"10.1126\/scisignal.2002962","article-title":"The Rho exchange factors Vav2 and Vav3 control a lung metastasis-specific transcriptional program in breast cancer cells","volume":"5","author":"Citterio","year":"2012","journal-title":"Sci. Signal"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e71","DOI":"10.1093\/nar\/gkv1507","article-title":"TCGAbiolinks: an R\/Bioconductor package for integrative analysis of TCGA data","volume":"44","author":"Colaprico","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.ccell.2018.01.001","article-title":"RHOAG17V induces T follicular helper cell specification and promotes lymphomagenesis","volume":"33","author":"Cortes","year":"2018","journal-title":"Cancer Cell"},{"key":"B18","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1038\/nrc1819","article-title":"Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis","volume":"6","author":"Cully","year":"2006","journal-title":"Nat. Reviews Cancer"},{"key":"B19","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/ejhg.2013.130","article-title":"Severe forms of Baraitser-Winter syndrome are caused by ACTB mutations rather than ACTG1 mutations","volume":"22","author":"Di Donato","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.ccell.2017.03.007","article-title":"TIAM1 antagonizes TAZ\/YAP both in the destruction complex in the cytoplasm and in the nucleus to inhibit invasion of intestinal epithelial cells","volume":"31","author":"Diamantopoulou","year":"2017","journal-title":"Cancer Cell"},{"key":"B21","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1038\/bjc.2017.420","article-title":"Mechanisms of inactivation of the tumour suppressor gene RHOA in colorectal cancer","volume":"118","author":"Dopeso","year":"2018","journal-title":"Br. Journal Cancer"},{"key":"B22","doi-asserted-by":"publisher","first-page":"20235","DOI":"10.18632\/aging.103772","article-title":"ARHGEF11 promotes proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma through activation of beta-catenin pathway","volume":"12","author":"Du","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"B23","doi-asserted-by":"publisher","first-page":"4580","DOI":"10.1038\/sj.onc.1210244","article-title":"Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth","volume":"26","author":"Durkin","year":"2007","journal-title":"Oncogene"},{"key":"B24","doi-asserted-by":"publisher","first-page":"351","DOI":"10.3390\/cells8040351","article-title":"p190RhoGAPs, the ARHGAP35- and ARHGAP5-encoded proteins, in health and disease","volume":"8","author":"H\u00e9raud","year":"2019","journal-title":"Cells"},{"key":"B25","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.cell.2012.06.024","article-title":"A landscape of driver mutations in melanoma","volume":"150","author":"Hodis","year":"2012","journal-title":"Cell"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1126\/science.278.5342.1464","article-title":"Inhibition of invasion of epithelial cells by Tiam1-Rac signaling","volume":"278","author":"Hordijk","year":"1997","journal-title":"Science"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1002\/humu.22350","article-title":"Functional analysis of a de novo ACTB mutation in a patient with atypical Baraitser-Winter syndrome","volume":"34","author":"Johnston","year":"2013","journal-title":"Hum. Mutat."},{"key":"B28","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/ng.2984","article-title":"Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma","volume":"46","author":"Kakiuchi","year":"2014","journal-title":"Nat. Genet."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1038\/ng.2359","article-title":"Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma","volume":"44","author":"Krauthammer","year":"2012","journal-title":"Nat. Genet"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3826","DOI":"10.1158\/0008-5472.can-15-2923","article-title":"Rho GTPase transcriptome analysis reveals oncogenic roles for rho GTPase-Activating proteins in basal-like breast cancers","volume":"76","author":"Lawson","year":"2016","journal-title":"Cancer Research"},{"key":"B31","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3390\/biom15010003","article-title":"The expression regulation and cancer-promoting roles of RACGAP1","volume":"15","author":"Lin","year":"2024","journal-title":"Biomolecules"},{"key":"B32","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.ccell.2019.05.015","article-title":"RAC1 P29S induces a mesenchymal phenotypic switch via serum response factor to promote melanoma development and therapy resistance","volume":"36","author":"Lionarons","year":"2019","journal-title":"Cancer Cell"},{"key":"B33","doi-asserted-by":"publisher","first-page":"271","DOI":"10.2147\/jhc.s298554","article-title":"ARHGAP20 expression inhibited HCC progression by regulating the PI3K-AKT signaling pathway","volume":"8","author":"Liu","year":"2021","journal-title":"J. Hepatocell. Carcinoma"},{"key":"B34","doi-asserted-by":"publisher","first-page":"116118","DOI":"10.1016\/j.biopha.2023.116118","article-title":"MYH9: a key protein involved in tumor progression and virus-related diseases","volume":"171","author":"Liu","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"B35","doi-asserted-by":"publisher","first-page":"4788","DOI":"10.1038\/s41467-020-18524-3","article-title":"VAV2 signaling promotes regenerative proliferation in both cutaneous and head and neck squamous cell carcinoma","volume":"11","author":"Lorenzo-Mart\u00edn","year":"","journal-title":"Nat. Communications"},{"key":"B36","doi-asserted-by":"publisher","first-page":"5098","DOI":"10.1038\/s41388-020-1353-x","article-title":"Vav2 pharmaco-mimetic mice reveal the therapeutic value and caveats of the catalytic inactivation of a Rho exchange factor","volume":"39","author":"Lorenzo-Mart\u00edn","year":"","journal-title":"Oncogene"},{"key":"B37","doi-asserted-by":"publisher","first-page":"3341","DOI":"10.1038\/s41388-022-02341-7","article-title":"The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function","volume":"41","author":"Lorenzo-Mart\u00edn","year":"2022","journal-title":"Oncogene"},{"key":"B38","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.ydbio.2013.12.006","article-title":"Deletion of MgcRacGAP in the male germ cells impairs spermatogenesis and causes male sterility in the mouse","volume":"386","author":"Lores","year":"2014","journal-title":"Dev. Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1074\/jbc.m507582200","article-title":"The rac activator Tiam1 is a Wnt-responsive gene that modifies intestinal tumor development","volume":"281","author":"Malliri","year":"2006","journal-title":"J. Biological Chemistry"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.cell.2017.09.042","article-title":"Universal patterns of selection in cancer and somatic tissues","volume":"171","author":"Martincorena","year":"2017","journal-title":"Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1101\/gr.239244.118","article-title":"Maftools: efficient and comprehensive analysis of somatic variants in cancer","volume":"28","author":"Mayakonda","year":"2018","journal-title":"Genome Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"4288","DOI":"10.1093\/nar\/gks042","article-title":"Differential expression analysis of multifactor RNA-seq experiments with respect to biological variation","volume":"40","author":"Mccarthy","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"e1001615","DOI":"10.1371\/journal.pbio.1001615","article-title":"The Rho exchange factors Vav2 and Vav3 favor skin tumor initiation and promotion by engaging extracellular signaling loops","volume":"11","author":"Menacho-Marquez","year":"2013","journal-title":"PLoS Biol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"R41","DOI":"10.1186\/gb-2011-12-4-r41","article-title":"GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers","volume":"12","author":"Mermel","year":"2011","journal-title":"Genome Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"18517","DOI":"10.1038\/srep18517","article-title":"Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer","volume":"6","author":"Michaut","year":"2016","journal-title":"Sci. Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/s41556-020-0488-x","article-title":"Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions","volume":"22","author":"Muller","year":"2020","journal-title":"Nat. Cell Biology"},{"key":"B47","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1182\/blood-2015-06-644948","article-title":"Variegated RHOA mutations in adult T-cell leukemia\/lymphoma","volume":"127","author":"Nagata","year":"2016","journal-title":"Blood"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1038\/s41467-021-21898-7","article-title":"Integrated cross-study datasets of genetic dependencies in cancer","volume":"12","author":"Pacini","year":"2021","journal-title":"Nat. Communications"},{"key":"B49","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/ng.2873","article-title":"Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas","volume":"46","author":"Palomero","year":"2014","journal-title":"Nat. Genet"},{"key":"B50","doi-asserted-by":"publisher","first-page":"188517","DOI":"10.1016\/j.bbcan.2021.188517","article-title":"SOX9: an emerging driving factor from cancer progression to drug resistance","volume":"1875","author":"Panda","year":"2021","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"B51","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1080\/21541248.2016.1173767","article-title":"Deregulation of Rho GTPases in cancer","volume":"7","author":"Porter","year":"2016","journal-title":"Small GTPases"},{"key":"B52","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.ijbiomac.2021.04.022","article-title":"Tumor suppressor gene DLC1: its modifications, interactive molecules, and potential prospects for clinical cancer application","volume":"182","author":"Ren","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1186\/1471-2105-12-480","article-title":"GC-Content normalization for RNA-seq data","volume":"12","author":"Risso","year":"2011","journal-title":"BMC Bioinforma."},{"key":"B54","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1016\/j.ccell.2017.10.004","article-title":"A paradoxical tumor-suppressor role for the Rac1 exchange factor Vav1 in T cell acute lymphoblastic leukemia","volume":"32","author":"Robles-Valero","year":"2017","journal-title":"Cancer Cell"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e108125","DOI":"10.15252\/embj.2021108125","article-title":"Cancer-associated mutations in VAV1 trigger variegated signaling outputs and T-cell lymphomagenesis","volume":"40","author":"Robles-Valero","year":"2021","journal-title":"EMBO Journal"},{"key":"B56","doi-asserted-by":"publisher","first-page":"3533","DOI":"10.1002\/1878-0261.13295","article-title":"Characterization of the spectrum of trivalent VAV1-mutation-driven tumours using a gene-edited mouse model","volume":"16","author":"Robles-Valero","year":"2022","journal-title":"Mol. Oncol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"5808","DOI":"10.1038\/s41467-020-19489-z","article-title":"Vav2 catalysis-dependent pathways contribute to skeletal muscle growth and metabolic homeostasis","volume":"11","author":"Rodr\u00edguez-Fdez","year":"2020","journal-title":"Nat. Communications"},{"key":"B58","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1002\/gcc.22202","article-title":"Recurrent RHOA mutations in pediatric Burkitt lymphoma treated according to the NHL-BFM protocols","volume":"53","author":"Rohde","year":"2014","journal-title":"Genes, Chromosomesand Cancer"},{"key":"B59","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/ng.2872","article-title":"Somatic RHOA mutation in angioimmunoblastic T cell lymphoma","volume":"46","author":"Sakata-Yanagimoto","year":"2014","journal-title":"Nat. Genet"},{"key":"B60","doi-asserted-by":"publisher","first-page":"eadg5289","DOI":"10.1126\/scisignal.adg5289","article-title":"RHOA(L57V) drives the development of diffuse gastric cancer through IGF1R-PAK1-YAP1 signaling","volume":"16","author":"Schaefer","year":"2023","journal-title":"Sci. Signal"},{"key":"B61","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.cels.2018.03.003","article-title":"Pan-cancer alterations of the MYC oncogene and its proximal network across the cancer genome Atlas","volume":"6","author":"Schaub","year":"2018","journal-title":"Cell Syst."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1038\/ng.3382","article-title":"Exome sequencing of desmoplastic melanoma identifies recurrent NFKBIE promoter mutations and diverse activating mutations in the MAPK pathway","volume":"47","author":"Shain","year":"2015","journal-title":"Nat. Genet."},{"key":"B63","doi-asserted-by":"publisher","first-page":"7447","DOI":"10.1038\/s41388-019-0963-7","article-title":"Rho GTPases in cancer: friend or foe?","volume":"38","author":"Svensmark","year":"2019","journal-title":"Oncogene"},{"key":"B64","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.cell.2017.06.010","article-title":"Defining a cancer dependency map","volume":"170","author":"Tsherniak","year":"2017","journal-title":"Cell"},{"key":"B65","doi-asserted-by":"publisher","first-page":"4863","DOI":"10.1242\/jcs.01367","article-title":"The RacGEF Tiam1 inhibits migration and invasion of metastatic melanoma via a novel adhesive mechanism","volume":"117","author":"Uhlenbrock","year":"2004","journal-title":"J. Cell Sci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/nrm2882","article-title":"The emerging mechanisms of isoform-specific PI3K signalling","volume":"11","author":"Vanhaesebroeck","year":"2010","journal-title":"Nat. Reviews Mol. Cell Biology"},{"key":"B67","doi-asserted-by":"publisher","first-page":"11992","DOI":"10.1038\/s41598-019-48229-7","article-title":"Analysis of head and neck carcinoma progression reveals novel and relevant stage-specific changes associated with immortalisation and malignancy","volume":"9","author":"Veeramachaneni","year":"2019","journal-title":"Sci. Rep."},{"key":"B68","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"B69","doi-asserted-by":"publisher","first-page":"51829","DOI":"10.18632\/oncotarget.10386","article-title":"ARHGAP24 inhibits cell cycle progression, induces apoptosis and suppresses invasion in renal cell carcinoma","volume":"7","author":"Xu","year":"2016","journal-title":"Oncotarget"},{"key":"B70","doi-asserted-by":"publisher","first-page":"6189","DOI":"10.7150\/thno.72134","article-title":"ARHGAP24 represses beta-catenin transactivation-induced invasiveness in hepatocellular carcinoma mainly by acting as a GTPase-independent scaffold","volume":"12","author":"Yang","year":"2022","journal-title":"Theranostics"},{"key":"B71","doi-asserted-by":"publisher","first-page":"e73077","DOI":"10.1371\/journal.pone.0073077","article-title":"Tiam1 transgenic mice display increased tumor invasive and metastatic potential of colorectal cancer after 1,2-dimethylhydrazine treatment","volume":"8","author":"Yu","year":"2013","journal-title":"PloS One"},{"key":"B72","first-page":"2196","article-title":"Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC-1) homologous to rat RhoGAP","volume":"58","author":"Yuan","year":"1998","journal-title":"Cancer Research"},{"key":"B73","doi-asserted-by":"publisher","first-page":"3213","DOI":"10.1038\/onc.2016.473","article-title":"Rho GTPases: anti- or pro-neoplastic targets?","volume":"36","author":"Zandvakili","year":"2017","journal-title":"Oncogene"},{"key":"B74","doi-asserted-by":"publisher","first-page":"2998","DOI":"10.1172\/jci92026","article-title":"Mutations in 5-methylcytosine oxidase TET2 and RhoA cooperatively disrupt T cell homeostasis","volume":"127","author":"Zang","year":"2017","journal-title":"J. Clin. Invest"},{"key":"B75","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1158\/2159-8290.cd-19-0811","article-title":"Gain-of-Function RHOA mutations promote focal adhesion kinase activation and dependency in diffuse gastric cancer","volume":"10","author":"Zhang","year":"2020","journal-title":"Cancer Discovery"}],"container-title":["Frontiers in Bioinformatics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1708800\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:37:21Z","timestamp":1765953441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbinf.2025.1708800\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,17]]},"references-count":75,"alternative-id":["10.3389\/fbinf.2025.1708800"],"URL":"https:\/\/doi.org\/10.3389\/fbinf.2025.1708800","relation":{},"ISSN":["2673-7647"],"issn-type":[{"value":"2673-7647","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,17]]},"article-number":"1708800"}}