{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARHGEF39, a member of the Dbl‐family of guanine nucleotide exchange factors, mediates activation of the small GTPase Rac1 to regulate cytoskeletal reorganization and promote tumor progression. Its increased expression has been observed in several malignancies—including non‐small cell lung cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", hepatocellular carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", gastric cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and clear cell renal cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In these contexts, ARHGEF39 enhances cell proliferation, migration, invasion, and metastatic potential by stimulating downstream signaling cascades. For example, in lung cancer cells ARHGEF39 activates Rac1 to induce the expression of Cyclin A2, Cyclin D1, and MMP2 through the p38–ATF2 pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", while in gastric cancer and renal carcinoma, its overexpression correlates with increased Akt and ERK phosphorylation that drives tumorigenicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, ARHGEF39 operates in a nonredundant manner with other Rac-GEFs such as FARP1 and TIAM2 to control specific aspects of membrane ruffle formation in lung adenocarcinoma cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Beyond its oncogenic properties, noncoding regulatory variants altering ARHGEF39 expression have been linked to neurodevelopmental disorders such as specific language impairment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In several studies, elevated ARHGEF39 levels have also been associated with poor overall survival and enhanced metastatic risk, underscoring its potential as a prognostic biomarker."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Interestingly, differential detection in urinary extracellular vesicles—where ARHGEF39 was found exclusively in noncancer samples from bladder studies—further highlights a context-dependent role in cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Together, these findings position ARHGEF39 as a critical mediator of oncogenic signaling and a promising target for therapeutic intervention.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Haijing Zhou, Lin Cai, Xiupeng Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARHGEF39 promotes tumor progression via activation of Rac1/P38 MAPK/ATF2 signaling and predicts poor prognosis in non-small cell lung cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Lab Invest (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41374-018-0022-y"}], "href": "https://doi.org/10.1038/s41374-018-0022-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29382922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29382922"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Haixiao Wang, Yandong Li, Yuping Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C9orf100, a new member of the Dbl-family guanine nucleotide exchange factors, promotes cell proliferation and migration in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Med Rep (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/mmr.2012.783"}], "href": "https://doi.org/10.3892/mmr.2012.783"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22327280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22327280"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jian Gao, Wei-Dong Jia "}, {"type": "b", "children": [{"type": "t", "text": "Expression of Rho Guanine Nucleotide Exchange Factor 39 (ARHGEF39) and Its Prognostic Significance in Hepatocellular Carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Sci Monit (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12659/MSM.918270"}], "href": "https://doi.org/10.12659/MSM.918270"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31626606"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31626606"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Haixiao Wang, Miaomiao Li, Xiaobao Tao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ARHGEF39 promotes gastric cancer cell proliferation and migration via Akt signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-017-3153-3"}], "href": "https://doi.org/10.1007/s11010-017-3153-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28871449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28871449"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Shuzhong Wang, Yanmei Wang, Chuanyun Wang "}, {"type": "b", "children": [{"type": "t", "text": "Rho guanine nucleotide exchange factor 39 increases the viability, migration and invasion of clear cell renal cell carcinoma cells via the activation of the AKT/ERK signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Mol Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1590/1678-4685-GMB-2019-0383"}], "href": "https://doi.org/10.1590/1678-4685-GMB-2019-0383"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33231603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33231603"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mariana Cooke, Gabriel Kreider-Letterman, Martin J Baker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FARP1, ARHGEF39, and TIAM2 are essential receptor tyrosine kinase effectors for Rac1-dependent cell motility in human lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2021.109905"}], "href": "https://doi.org/10.1016/j.celrep.2021.109905"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34731623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34731623"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mariana Cooke "}, {"type": "b", "children": [{"type": "t", "text": "Novel insights into the RTK-dependent metastatic phenotype of KRAS-mutant lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Oncol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/23723556.2021.2013723"}], "href": "https://doi.org/10.1080/23723556.2021.2013723"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35419483"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35419483"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "P Devanna, X S Chen, J Ho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Next-gen sequencing identifies non-coding variation disrupting miRNA-binding sites in neurological disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mp.2017.30"}], "href": "https://doi.org/10.1038/mp.2017.30"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28289279"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28289279"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Baojin Xu, Wu Lv, Xiaoyan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prognostic genes of hepatocellular carcinoma based on gene coexpression network analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.28441"}], "href": "https://doi.org/10.1002/jcb.28441"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30775801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30775801"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Amparo Perez, Ana Loizaga, Raquel Arceo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Pilot Study on the Potential of RNA-Associated to Urinary Vesicles as a Suitable Non-Invasive Source for Diagnostic Purposes in Bladder Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancers (Basel) (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cancers6010179"}], "href": "https://doi.org/10.3390/cancers6010179"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24458310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24458310"}]}]}]}