{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:55:15Z","timestamp":1789124115970,"version":"build-2803163510"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2020A1515110581"],"award-info":[{"award-number":["2020A1515110581"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"start-up funds from Guangzhou University"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32071145 and 31771572"],"award-info":[{"award-number":["32071145 and 31771572"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nature Science Foundation of Jiangsu Province","award":["BK20191356"],"award-info":[{"award-number":["BK20191356"]}]},{"name":"Science and Technology Program of Guangzhou","award":["202201020209"],"award-info":[{"award-number":["202201020209"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The roles of Rho GTPases in various types of cancer have been extensively studied, but the research of Rho guanine nucleotide exchange factors (GEFs) in cancer is not comprehensive. Rho guanine nucleotide exchange factor 6 (ARHGEF6) is an important member of the Rho GEFs family involved in cytoskeletal rearrangement, and it has not been investigated in acute myeloid leukemia (AML). Our research showed that the expression of ARHGEF6 was mainly higher in AML cell lines, meanwhile, was highest in the samples from patients with AML compared to other cancer types. High ARHGEF6 expression in AML was associated with a good prognosis. ARHGEF6<jats:sup>low<\/jats:sup> cases showed significantly higher overall survival (OS) after autologous or allogeneic HSCT (auto\/allo-HSCT). High expression of ARHGEF6 downregulates the negative regulation of myeloid differentiation process and upregulates G protein-coupled receptor signaling pathway-related processes, among which HOXA9, HOXB6, and TRH have significant differential expression and prognostic impact in AML. Therefore, ARHGEF6 can become a prognostic marker in AML; ARHGEF6<jats:sup>low<\/jats:sup> patients can gain from auto\/allo-HSCT.<\/jats:p>","DOI":"10.1371\/journal.pone.0283934","type":"journal-article","created":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T17:33:52Z","timestamp":1680888832000},"page":"e0283934","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinical implication and potential function of ARHGEF6 in acute myeloid leukemia: An in vitro study"],"prefix":"10.1371","volume":"18","author":[{"given":"Kang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9346-9822","authenticated-orcid":true,"given":"Haiquan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaofan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7099-4528","authenticated-orcid":true,"given":"Jiankui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"issue":"21","key":"pone.0283934.ref001","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1182\/blood.V124.21.958.958","article-title":"Prevalence and incidence of acute myeloid leukemia may be higher than currently accepted estimates among the \u226565 year-old population in the United States","volume":"124","author":"S Turbeville","year":"2014","journal-title":"Blood"},{"issue":"12","key":"pone.0283934.ref002","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMra1406184","article-title":"Acute Myeloid Leukemia","volume":"373","author":"H Dohner","year":"2015","journal-title":"N Engl J Med"},{"issue":"1","key":"pone.0283934.ref003","article-title":"The role of ARHGAP9: clinical implication and potential function in acute myeloid leukemia","volume":"19","author":"C Han","year":"2021","journal-title":"Journal of Translational Medicine"},{"issue":"1","key":"pone.0283934.ref004","doi-asserted-by":"crossref","DOI":"10.1186\/s13000-019-0841-1","article-title":"BCL2 overexpression: clinical implication and biological insights in acute myeloid leukemia","volume":"14","author":"J Zhou","year":"2019","journal-title":"Diagnostic Pathology"},{"issue":"Pt 5","key":"pone.0283934.ref005","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1242\/jcs.01660","article-title":"The Ras superfamily at a glance","volume":"118","author":"K Wennerberg","year":"2005","journal-title":"J Cell Sci"},{"issue":"9","key":"pone.0283934.ref006","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/nrm2476","article-title":"Mammalian Rho GTPases: new insights into their functions from in vivo studies","volume":"9","author":"SJ Heasman","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"Pt 7","key":"pone.0283934.ref007","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1242\/jcs.03428","article-title":"Rho activation at a glance","volume":"120","author":"RJ Buchsbaum","year":"2007","journal-title":"J Cell Sci"},{"issue":"Pt 23","key":"pone.0283934.ref008","doi-asserted-by":"crossref","first-page":"5457","DOI":"10.1242\/jcs.01582","article-title":"Rho signalling at a glance","volume":"117","author":"M. Schwartz","year":"2004","journal-title":"J Cell Sci"},{"issue":"1","key":"pone.0283934.ref009","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1152\/physrev.00045.2020","article-title":"Rho GTPase signaling in cancer progression and dissemination","volume":"102","author":"E Crosas-Molist","year":"2022","journal-title":"Physiol Rev"},{"issue":"Pt 2","key":"pone.0283934.ref010","first-page":"400","article-title":"The RhoGAP ARHGAP19 controls cytokinesis and chromosome segregation in T lymphocytes","volume":"127","author":"MD David","year":"2014","journal-title":"J Cell Sci"},{"issue":"5","key":"pone.0283934.ref011","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.stem.2012.04.007","article-title":"Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation","volume":"10","author":"MC Florian","year":"2012","journal-title":"Cell Stem Cell"},{"issue":"5","key":"pone.0283934.ref012","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1182\/blood-2009-09-198127","article-title":"Rho GTPases in hematopoiesis and hemopathies","volume":"115","author":"JC Mulloy","year":"2010","journal-title":"Blood"},{"issue":"1","key":"pone.0283934.ref013","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1182\/blood-2005-05-2171","article-title":"Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem\/progenitor cell survival, adhesion, and engraftment","volume":"107","author":"L Wang","year":"2006","journal-title":"Blood"},{"issue":"12","key":"pone.0283934.ref014","doi-asserted-by":"crossref","first-page":"5091","DOI":"10.1073\/pnas.0610819104","article-title":"Rho GTPase Cdc42 coordinates hematopoietic stem cell quiescence and niche interaction in the bone marrow","volume":"104","author":"L Yang","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0283934.ref015","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3389\/fcell.2020.00201","article-title":"Targeting Rac and Cdc42 GEFs in Metastatic Cancer.","volume":"8","author":"M Maldonado","year":"2020","journal-title":"Front Cell Dev Biol"},{"issue":"2","key":"pone.0283934.ref016","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.cellsig.2011.08.011","article-title":"Rac signaling in breast cancer: a tale of GEFs and GAPs","volume":"24","author":"E Wertheimer","year":"2012","journal-title":"Cell Signal"},{"issue":"3","key":"pone.0283934.ref017","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1080\/21541248.2016.1173767","article-title":"Deregulation of Rho GTPases in cancer","volume":"7","author":"AP Porter","year":"2016","journal-title":"Small GTPases"},{"issue":"20","key":"pone.0283934.ref018","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.1158\/0008-5472.CAN-17-1456","article-title":"The Rac GTPase in Cancer: From Old Concepts to New Paradigms","volume":"77","author":"MG Kazanietz","year":"2017","journal-title":"Cancer Res"},{"issue":"2","key":"pone.0283934.ref019","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/hmg\/ddg019","article-title":"Interaction of alphaPIX (ARHGEF6) with beta-parvin (PARVB) suggests an involvement of alphaPIX in integrin-mediated signaling","volume":"12","author":"G Rosenberger","year":"2003","journal-title":"Hum Mol Genet"},{"issue":"8","key":"pone.0283934.ref020","doi-asserted-by":"crossref","first-page":"6879","DOI":"10.1074\/jbc.M412119200","article-title":"\u03b1PIX Associates with Calpain 4, the Small Subunit of Calpain, and Has a Dual Role in Integrin-mediated Cell Spreading","volume":"280","author":"G Rosenberger","year":"2005","journal-title":"Journal of Biological Chemistry"},{"issue":"1","key":"pone.0283934.ref021","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00401-005-1085-6","article-title":"Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, \u03b1-PIX and sorcin","volume":"111","author":"T Yokota","year":"2006","journal-title":"Acta Neuropathologica"},{"issue":"2","key":"pone.0283934.ref022","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/tpj.2009.49","article-title":"Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells","volume":"10","author":"AK Maiti","year":"2010","journal-title":"The pharmacogenomics journal"},{"issue":"50","key":"pone.0283934.ref023","doi-asserted-by":"crossref","first-page":"29974","DOI":"10.1074\/jbc.M115.678003","article-title":"Cyclic Nucleotide-dependent Protein Kinases Target ARHGAP17 and ARHGEF6 Complexes in Platelets","volume":"290","author":"Z Nagy","year":"2015","journal-title":"J Biol Chem"},{"issue":"1","key":"pone.0283934.ref024","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/pro.3307","article-title":"The human protein atlas: A spatial map of the human proteome","volume":"27","author":"PJ Thul","year":"2018","journal-title":"Protein Sci"},{"issue":"7391","key":"pone.0283934.ref025","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nature11003","article-title":"The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity","volume":"483","author":"J Barretina","year":"2012","journal-title":"Nature"},{"issue":"8","key":"pone.0283934.ref026","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.neo.2017.05.002","article-title":"UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses","volume":"19","author":"DS Chandrashekar","year":"2017","journal-title":"Neoplasia"},{"issue":"W1","key":"pone.0283934.ref027","doi-asserted-by":"crossref","first-page":"W98","DOI":"10.1093\/nar\/gkx247","article-title":"GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses","volume":"45","author":"Z Tang","year":"2017","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"pone.0283934.ref028","doi-asserted-by":"crossref","first-page":"D956","DOI":"10.1093\/nar\/gkx1090","article-title":"LinkedOmics: analyzing multi-omics data within and across 32 cancer types","volume":"46","author":"SV Vasaikar","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"22","key":"pone.0283934.ref029","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1056\/NEJMoa1301689","article-title":"Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia","volume":"368","author":"TJ Ley","year":"2013","journal-title":"N Engl J Med"},{"issue":"12","key":"pone.0283934.ref030","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/S0968-0004(01)01973-9","article-title":"Dbl family guanine nucleotide exchange factors","volume":"26","author":"Y. Zheng","year":"2001","journal-title":"Trends Biochem Sci"},{"issue":"2","key":"pone.0283934.ref031","doi-asserted-by":"crossref","first-page":"11169","DOI":"10.1080\/21655979.2021.2006519","article-title":"Role of Rho guanine nucleotide exchange factors in non-small cell lung cancer","volume":"12","author":"RJ Zeng","year":"2021","journal-title":"Bioengineered"},{"issue":"4","key":"pone.0283934.ref032","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1080\/21541248.2018.1423851","article-title":"Rho guanosine nucleotide exchange factors are not such bad guys after all in cancer","volume":"11","author":"J Robles-Valero","year":"2020","journal-title":"Small GTPases"},{"issue":"1","key":"pone.0283934.ref033","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.bbrc.2010.03.148","article-title":"DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma","volume":"395","author":"L Wang","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"issue":"24","key":"pone.0283934.ref034","doi-asserted-by":"crossref","first-page":"6088","DOI":"10.7150\/jca.33244","article-title":"High expression of DOCK2 indicates good prognosis in acute myeloid leukemia","volume":"10","author":"N Hu","year":"2019","journal-title":"J Cancer"},{"issue":"5","key":"pone.0283934.ref035","doi-asserted-by":"crossref","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":"Z Diamantopoulou","year":"2017","journal-title":"Cancer Cell"},{"issue":"4","key":"pone.0283934.ref036","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.3892\/or.2015.3785","article-title":"Overexpression of Tiam1 promotes the progression of laryngeal squamous cell carcinoma","volume":"33","author":"S Wang","year":"2015","journal-title":"Oncol Rep"},{"issue":"5","key":"pone.0283934.ref037","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.3892\/ol.2016.5091","article-title":"Clinical implication of Tiam1 overexpression in the prognosis of patients with serous ovarian carcinoma","volume":"12","author":"H Li","year":"2016","journal-title":"Oncol Lett"},{"issue":"9","key":"pone.0283934.ref038","doi-asserted-by":"crossref","first-page":"e258","DOI":"10.1038\/oncsis.2016.59","article-title":"The Rho guanine nucleotide exchange factor ARHGEF5 promotes tumor malignancy via epithelial-mesenchymal transition","volume":"5","author":"Y Komiya","year":"2016","journal-title":"Oncogenesis"},{"issue":"1","key":"pone.0283934.ref039","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s13046-018-0729-z","article-title":"miR-148b-3p inhibits gastric cancer metastasis by inhibiting the Dock6\/Rac1\/Cdc42 axis","volume":"37","author":"X Li","year":"2018","journal-title":"J Exp Clin Cancer Res"},{"key":"pone.0283934.ref040","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1477-7800-5-23","article-title":"The expression and prognostic value of the guanine nucleotide exchange factors (GEFs) Trio, Vav1 and TIAM-1 in human breast cancer","volume":"5","author":"J Lane","year":"2008","journal-title":"Int Semin Surg Oncol"},{"issue":"19","key":"pone.0283934.ref041","doi-asserted-by":"crossref","first-page":"3951","DOI":"10.1242\/dev.068346","article-title":"The regulation of Hox gene expression during animal development","volume":"140","author":"M Mallo","year":"2013","journal-title":"Development (Cambridge)"},{"issue":"6","key":"pone.0283934.ref042","doi-asserted-by":"crossref","first-page":"438","DOI":"10.2174\/1389202920666191017163837","article-title":"Hematopoietic Differentiation of Human Pluripotent Stem Cells: HOX and GATA Transcription Factors as Master Regulators.","volume":"20","author":"K Alsayegh","year":"2019","journal-title":"Curr Genomics"},{"issue":"3","key":"pone.0283934.ref043","doi-asserted-by":"crossref","first-page":"475","DOI":"10.2217\/fon.13.195","article-title":"Hox gene dysregulation in acute myeloid leukemia","volume":"10","author":"E De Braekeleer","year":"2014","journal-title":"Future oncology (London, England)"},{"issue":"11","key":"pone.0283934.ref044","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1038\/leu.2008.198","article-title":"HOX expression patterns identify a common signature for favorable AML","volume":"22","author":"M ANDREEFF","year":"2008","journal-title":"Leukemia"},{"issue":"4","key":"pone.0283934.ref045","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1182\/blood-2004-04-1583","article-title":"HOXB6 overexpression in murine bone marrow immortalizes a myelomonocytic precursor in vitro and causes hematopoietic stem cell expansion and acute myeloid leukemia in vivo","volume":"105","author":"NA Fischbach","year":"2005","journal-title":"Blood"},{"issue":"4","key":"pone.0283934.ref046","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1007\/s11684-021-0836-7","article-title":"Clinical significance of CD34(+)CD117(dim)\/CD34(+)CD117(bri) myeloblast-associated gene expression in t(8;21) acute myeloid leukemia","volume":"15","author":"X Li","year":"2021","journal-title":"Front Med"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0283934","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T17:34:29Z","timestamp":1680888869000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0283934"}},"subtitle":[],"editor":[{"given":"Senthilnathan","family":"Palaniyandi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,4,7]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0283934","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,7]]}}}